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Ryu HE, Heo SJ, Lee JH, Park B, Han T, Kwon YJ. Data-driven cluster analysis of lipids, inflammation, and aging in relation to new-onset type 2 diabetes mellitus. Endocrine 2025; 88:151-161. [PMID: 39743640 DOI: 10.1007/s12020-024-04154-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 12/27/2024] [Indexed: 01/04/2025]
Abstract
PURPOSE Early detection and intervention are vital for managing type 2 diabetes mellitus (T2DM) effectively. However, it's still unclear which risk factors for T2DM onset are most significant. This study aimed to use cluster analysis to categorize individuals based on six known risk factors, helping to identify high-risk groups requiring early intervention to prevent T2DM onset. METHODS This study comprised 7402 Korean Genome and Epidemiology Study individuals aged 40 to 69 years. The hybrid hierarchical k-means clustering algorithm was employed on six variables normalized by Z-score-age, triglycerides, total cholesterol, non-high-density lipoprotein cholesterol, high-density lipoprotein cholesterol and C-reactive protein. Multivariable Cox proportional hazard regression analyses were conducted to assess T2DM incidence. RESULTS Four distinct clusters with significantly different characteristics and varying risks of new-onset T2DM were identified. Cluster 4 (insulin resistance) had the highest T2DM incidence, followed by Cluster 3 (inflammation and aging). Clusters 3 and 4 exhibited significantly higher T2DM incidence rates compared to Clusters 1 (healthy metabolism) and 2 (young age), even after adjusting for covariates. However, no significant difference was found between Clusters 3 and 4 after covariate adjustment. CONCLUSION Clusters 3 and 4 showed notably higher T2DM incidence rates, emphasizing the distinct risks associated with insulin resistance and inflammation-aging clusters.
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Affiliation(s)
- Ha-Eun Ryu
- Department of Family Medicine, Yongin Severance Hospital, Gyeonggi-do, Republic of Korea
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seok-Jae Heo
- Division of Biostatistics, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jong Hee Lee
- Department of Family Medicine, Yongin Severance Hospital, Gyeonggi-do, Republic of Korea
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Byoungjin Park
- Department of Family Medicine, Yongin Severance Hospital, Gyeonggi-do, Republic of Korea
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Taehwa Han
- Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yu-Jin Kwon
- Department of Family Medicine, Yongin Severance Hospital, Gyeonggi-do, Republic of Korea.
- Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Wu X, Zhang Z, Li J, Zong J, Yuan L, Shu L, Cheong LY, Huang X, Jiang M, Ping Z, Xu A, Hoo RL. Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2408763. [PMID: 39985288 PMCID: PMC12005791 DOI: 10.1002/advs.202408763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 12/30/2024] [Indexed: 02/24/2025]
Abstract
Dysregulation of adipose tissue (AT) homeostasis in obesity contributes to metabolic stress and disorders. Here, we identified that Coiled-coil-helix-coiled-coil-helix domain containing 10 (Chchd10) is a novel regulator of AT remodeling upon excess energy intake. Chchd10 is significantly reduced in the white adipose tissue (WAT) of mice in response to high-fat diet (HFD) feeding. AT-Chchd10 deficiency accelerates adipogenesis predominantly in subcutaneous AT of mice to store excess energy in response to short-term HFD feeding while upregulates glutathione S-transferase A4 (GSTA4) to facilitate 4-HNE clearance mainly in visceral AT to prevent protein carbonylation-induced cell dysfunction after long-term HFD feeding. Hence, Chchd10 deficiency attenuates diet-induced obesity and related metabolic disorders in mice. Mechanistically, Chchd10 deficiency enhances adipogenesis and GSTA4 expression by activating TDP43/Raptor/p62/Keap1/NRF2 axis. Notably, the beneficial effect of Chchd10 deficiency is eliminated in hypertrophic adipocytes, where p62 is strikingly reduced. Collectively, Chchd10 is a metabolic sensor maintaining AT homeostasis, and the loss of p62 in adipose tissue under obese conditions impairs Chchd10-mediated AT remodeling.
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Affiliation(s)
- Xiaoping Wu
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of Pharmacology and PharmacyThe University of Hong KongHong Kong SARChina
| | - Zixuan Zhang
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of Pharmacology and PharmacyThe University of Hong KongHong Kong SARChina
| | - Jingjing Li
- Department of Rehabilitation SciencesFaculty of Health and Social SciencesHong Kong Polytechnic UniversityHong Kong SARChina
| | - Jiuyu Zong
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of Pharmacology and PharmacyThe University of Hong KongHong Kong SARChina
| | - Lufengzi Yuan
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of Pharmacology and PharmacyThe University of Hong KongHong Kong SARChina
| | - Lingling Shu
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerDepartment of Hematological OncologySun Yat‐sen University Cancer CenterChina
- Department of MedicineThe University of Hong KongHong Kong SARChina
| | - Lai Yee Cheong
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of MedicineThe University of Hong KongHong Kong SARChina
| | - Xiaowen Huang
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of Pharmacology and PharmacyThe University of Hong KongHong Kong SARChina
| | - Mengxue Jiang
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of Pharmacology and PharmacyThe University of Hong KongHong Kong SARChina
| | - Zhihui Ping
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of Pharmacology and PharmacyThe University of Hong KongHong Kong SARChina
| | - Aimin Xu
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of MedicineThe University of Hong KongHong Kong SARChina
| | - Ruby L.C. Hoo
- State Key Laboratory of Pharmaceutical BiotechnologyThe University of Hong KongHong Kong SARChina
- Department of Pharmacology and PharmacyThe University of Hong KongHong Kong SARChina
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Wang ZZ, Xu Q, Zhang YH, Wu RR, Cui JL, Zhou J, Hong JF. Oxidative balance score is associated with increased risk of sarcopenia and sarcopenic obesity in non-elderly adults: results from NHANES 2011-2018. Nutr Metab (Lond) 2025; 22:23. [PMID: 40069772 PMCID: PMC11899308 DOI: 10.1186/s12986-025-00914-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 03/03/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Sarcopenia and obesity, two prevalent health conditions, often coexist and exacerbate each other's impact, increasing the risk of chronic diseases and mortality. This dual condition is termed "sarcopenic obesity." The correlation between oxidative stress (OS) and sarcopenia or obesity was established, and the oxidative balance score (OBS) can serve as an indicator of overall dietary or lifestyle-related OS exposure within an individual. Prior reports have not addressed the relationship between OBS and sarcopenia or sarcopenic obesity in adults under 60. This study endeavors to explore these associations and to identify potential dietary and lifestyle risk factors. METHODS We performed a cross-sectional analysis utilizing data from 4,241 participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. OBS is a cumulative score derived from 16 dietary components and 4 lifestyle components, where higher scores indicate greater exposure to antioxidants and lower exposure to pro-oxidant factors, reflecting a reduced oxidative stress burden. Weighted multivariate logistic regression was employed to investigate the association of OBS and sarcopenia and sarcopenic obesity. Further subgroup analyses was conducted to examine interactions with various covariates. The least absolute shrinkage and selection operator (LASSO) regression was applied to identify significant components of OBS associated with sarcopenia and sarcopenic obesity, which were subsequently integrated into a risk prediction nomogram model. The model's predictive accuracy was evaluated using the receiver operating characteristic (ROC) curve. RESULTS After adjusting for potential confounders, the weighted logistic regression analyses demonstrated a significant negative association between OBS and the prevalence of sarcopenia (odds ratio [OR] = 0.954, 95% confidence interval [CI] = 0.925-0.984, P = 0.004) and sarcopenic obesity (OR = 0.948, 95% CI = 0.918-0.980, P = 0.002). The nomogram models, informed by key OBS components identified through LASSO regression, exhibited considerable predictive value for sarcopenia (area under the ROC curve [AUC] = 0.813, 95% CI = 0.792-0.833) and sarcopenic obesity (AUC = 0.894, 95% CI = 0.879-0.909). CONCLUSION This study reveals a robust inverse correlation between OBS and both sarcopenia and sarcopenic obesity in adults aged 20-59. These results suggest that an antioxidant-rich diet and healthy lifestyle practices, including low-fat diets, adequate vitamin B intake, regular physical activity, and weight management, may help mitigate the risk of sarcopenia and sarcopenic obesity. Further research is warranted to confirm these associations and determine causality.
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Affiliation(s)
- Zhu-Zhu Wang
- The First Affiliated Hospital of Anhui Medical University, No, 218 Ji Xi Road, Shu Shan District, Hefei City, Anhui Province, 230022, China
- School of Nursing, Anhui Medical University, No. 81 Mei Shan Road, Shu Shan District, Hefei City, Anhui Province, 230032, China
| | - Qin Xu
- School of Nursing, Anhui Medical University, No. 81 Mei Shan Road, Shu Shan District, Hefei City, Anhui Province, 230032, China
| | - Yu-Han Zhang
- School of Nursing, Anhui Medical University, No. 81 Mei Shan Road, Shu Shan District, Hefei City, Anhui Province, 230032, China
| | - Rong-Rong Wu
- School of Nursing, Anhui Medical University, No. 81 Mei Shan Road, Shu Shan District, Hefei City, Anhui Province, 230032, China
| | - Jun-Ling Cui
- School of Nursing, Anhui Medical University, No. 81 Mei Shan Road, Shu Shan District, Hefei City, Anhui Province, 230032, China
| | - Ji Zhou
- School of Nursing, Anhui Medical University, No. 81 Mei Shan Road, Shu Shan District, Hefei City, Anhui Province, 230032, China
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Mei Shan Road, Shu Shan District, Hefei City, Anhui Province, 2300032, China
| | - Jing-Fang Hong
- School of Nursing, Anhui Medical University, No. 81 Mei Shan Road, Shu Shan District, Hefei City, Anhui Province, 230032, China.
- Nursing International Collaboration Research Center of Anhui Province, Hefei City, Anhui Province, 230601, China.
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Stumpf MAM, Cercato C, de Melo ME, Mancini MC. Sheer drop ahead: reviewing sarcopenia outcomes in elderly patients undergoing bariatric surgery. Rev Endocr Metab Disord 2025:10.1007/s11154-025-09946-9. [PMID: 39920515 DOI: 10.1007/s11154-025-09946-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/24/2025] [Indexed: 02/09/2025]
Abstract
The global prevalence of obesity among elderly patients continues to rise. Despite the availability of new antiobesity medications, bariatric surgery remains an effective treatment option for carefully selected candidates. However, it is not risk-free, especially in a vulnerable population, predisposing to falls, fractures and sarcopenia. Following bariatric surgery, there is rapid loss of muscle mass, particularly within the first 3 months. Muscle quality, on the other hand, characterized by functionality and indirectly assessed through strength tests, appears to be preserved. This is attributed to reductions in ectopic intramuscular fat deposits. Strategies to mitigate muscle loss and functional impairment include combined exercises (resistive and aerobic training), adequate protein and vitamin D intake, beta-hydroxy-beta-methylbutyrate (HMB) supplementation, and testosterone replacement therapy for men with confirmed hypogonadism. It is important to emphasize that, to date, no specific trial has evaluated the current sarcopenia criteria in elderly patients undergoing bariatric surgery. Therefore, future studies are needed to assess this particularly vulnerable population, not only to monitor changes in muscular health, but also to develop strategies for preventing therapeutic inertia.
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Affiliation(s)
- Matheo Augusto Morandi Stumpf
- Obesity Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School Hospital, R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo, SP 05403-010, Brazil.
| | - Cintia Cercato
- Obesity Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School Hospital, R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo, SP 05403-010, Brazil
| | - Maria E de Melo
- Obesity Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School Hospital, R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo, SP 05403-010, Brazil
| | - Marcio C Mancini
- Obesity Unit, Division of Endocrinology and Metabolism, University of São Paulo Medical School Hospital, R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo, SP 05403-010, Brazil
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Li Q, Wang L. Navigating the complex role of senescence in liver disease. Chin Med J (Engl) 2024; 137:3061-3072. [PMID: 39679454 PMCID: PMC11706581 DOI: 10.1097/cm9.0000000000003439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Indexed: 12/17/2024] Open
Abstract
ABSTRACT Cellular senescence, an irreversible state of cell cycle arrest characterized by phenotypic changes and a specific secretory profile, plays a dual role in liver health and disease. Under physiological conditions, senescence aids organ repair and regeneration, but its accumulation due to aging or pathological stress significantly contributes to chronic liver diseases, including alcoholic liver disease, metabolic dysfunction-associated steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Senescence is identified by a range of cellular and molecular changes, such as morphological alterations, expression of cell cycle inhibitors, senescence-associated β-galactosidase activity, and nuclear membrane changes. The onset of senescence in organ cells can affect the entire organism, primarily through the senescence-associated secretory phenotype, which has autocrine, paracrine, and endocrine effects on tissue microenvironments. The objective of this review is to offer a contemporary overview of the pathophysiological events involving hepatic senescent cells and to elucidate their role in the onset and progression of liver diseases, particularly through mechanisms like telomere shortening, genomic and mitochondrial DNA damage, and inflammation. Additionally, this review discusses the emerging senolytic therapies aimed at targeting senescent cells to delay or mitigate liver disease progression. The therapeutic potential of these interventions, alongside their safety and effectiveness, highlights the need for further research to refine these approaches and address unresolved problems in the field of hepatic cellular senescence.
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Affiliation(s)
- Qiuting Li
- Department of Hepatobiliary Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China
| | - Lin Wang
- Department of Hepatobiliary Surgery, Xi-Jing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China
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Byun KA, Seo SB, Oh S, Jang JW, Son KH, Byun K. Poly-D,L-Lactic Acid Fillers Increase Subcutaneous Adipose Tissue Volume by Promoting Adipogenesis in Aged Animal Skin. Int J Mol Sci 2024; 25:12739. [PMID: 39684448 DOI: 10.3390/ijms252312739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 11/23/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
During aging, subcutaneous white adipose tissue (sWAT) thickness and the adipogenic potential of adipose-derived stem cells (ASCs) decline. Poly-D,L-lactic acid (PDLLA) fillers are commonly used to restore diminished facial volume. Piezo1 increases polarizing macrophages towards the M2 phenotype, which promotes the secretion of fibroblast growth factor 2 (FGF2), thereby increasing ASC survival. This study evaluated whether PDLLA enhances adipogenesis in ASCs by modulating M2 polarization in an in vitro senescence model and in aged animals. Lipopolysaccharide (LPS)-induced senescent macrophages showed decreased Piezo1, which was upregulated by PDLLA. CD163 (an M2 marker) and FGF2 were downregulated in senescent macrophages but were upregulated by PDLLA. We evaluated whether reduced FGF2 secretion from senescent macrophages affects ASCs by applying conditioned media (CM) from macrophage cultures to ASCs. CM from senescent macrophages decreased ERK1/2 and proliferation in ASCs, both of which were restored by CM from PDLLA-stimulated senescent macrophages. Adipogenesis inducers (PPAR-γ and C/EBP-α) were downregulated by CM from senescent macrophages but upregulated by CM from PDLLA-stimulated senescent macrophages in ASCs. Similar patterns were observed in aged animal adipose tissue. PDLLA increased Piezo1 activity, M2 polarization, and FGF2 levels. PDLLA also enhanced ERK1/2, cell proliferation, PPAR-γ, and C/EBP-α expression, leading to increased adipose tissue thickness. In conclusion, our study showed that PDLLA increased adipose tissue thickness by modulating adipogenesis.
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Affiliation(s)
- Kyung-A Byun
- Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea
- LIBON Inc., Incheon 22006, Republic of Korea
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
| | - Suk Bae Seo
- SeoAh Song Dermatologic Clinic, Seoul 05557, Republic of Korea
| | - Seyeon Oh
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
| | - Jong-Won Jang
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health & Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea
| | - Kuk Hui Son
- Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Republic of Korea
| | - Kyunghee Byun
- Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
- Department of Health Sciences and Technology, Gachon Advanced Institute for Health & Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea
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Dong H, Cheng H, Xiong J, Liu L, Huang Y, Shan X, Fan H, Wang X, Wang X, Xiao P, Chen F, Mi J. Body fat variation and redistribution across different stages of life measured by dual-energy x-ray absorptiometry. J Glob Health 2024; 14:04247. [PMID: 39545353 PMCID: PMC11565468 DOI: 10.7189/jogh.14.04247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2024] Open
Abstract
Background The global obesity epidemic of all ages has increased the demand for accurate management of body fat in each stage of life. The primary aim of this study was to provide reference centiles of body fat indices for Chinese children and adults and compare those with ethnicities from USA using dual-energy x-ray absorptiometry (DXA). Methods The samples were drawn from two nationwide cross-sectional surveys of China Body Composition Life-course Study (2013-2023) and the US National Health and Nutrition Examination Survey (2011-2018). Age- and sex-specific centile curves were generated for a set of fat measurements, including total fat mass (FM), fat mass index (FMI), body fat percentage (BF%), trunk-to-leg fat ratio (TLR), android-to-gynoid fat ratio (AGR) and visceral-to-subcutaneous fat ratio (VSR), using the general additive model for location scale and shape method. Results The age-related variations from childhood to adulthood were generally similar among Chinese, Non-Hispanic Whites, Non-Hispanic Blacks and Mexican American population, with distinct levels across races and ethnicities. For whole-body fat (FM, FMI, and BF%), Mexican American population consistently presented the highest levels before 40 years old, followed by Non-Hispanic White, Non-Hispanic Black and Chinese individuals. For central fats indices, although the TLR and AGR levels in Chinese males were second to Mexican American counterparts in most stages of life, the VSR was much higher in Chinese than other races and ethnicities from eight years old. Conclusions DXA-based centiles for body fat quantity and distribution in Chinese population aged 3-60 years old were presented, and their differences with other race and ethnicity were noted across periods from early childhood to middle adulthood. Our findings will promote age-, sex- and ethnic-specific assessment of life-course body fat and obesity-related risks in clinical practice.
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Affiliation(s)
- Hongbo Dong
- Center for Noncommunicable Disease Management, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Hong Cheng
- Department of Epidemiology, Capital Institute of Pediatrics, Beijing, China
| | - Jingfan Xiong
- Child and Adolescent Chronic Disease Prevention and Control Department, Shenzhen Center for Chronic Disease Control, Shenzhen, China
| | - Li Liu
- School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China
| | - Yiwen Huang
- Center for Noncommunicable Disease Management, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
- Child Healthcare Center, Children’s Hospital, Capital Institute of Pediatrics, Beijing, China
| | - Xinying Shan
- Department of Epidemiology, Capital Institute of Pediatrics, Beijing, China
| | - Hongmin Fan
- North China University of Science and Technology, Hebei, Tangshan, China
| | - Xi Wang
- Center for Noncommunicable Disease Management, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Xia Wang
- Center for Noncommunicable Disease Management, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Pei Xiao
- Center for Noncommunicable Disease Management, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Fangfang Chen
- Department of Epidemiology, Capital Institute of Pediatrics, Beijing, China
| | - Jie Mi
- Center for Noncommunicable Disease Management, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
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Damanti S, Citterio L, Zagato L, Brioni E, Magnaghi C, Simonini M, De Lorenzo R, Ruggiero M, Santoro S, Senini E, Messina M, Vitali G, Manunta P, Manfredi AA, Lanzani C, Rovere Querini P. DNA polymorphisms in inflammatory and endocrine signals linked to frailty are also associated with obesity: data from the FRASNET cohort. Front Endocrinol (Lausanne) 2024; 15:1412160. [PMID: 39464190 PMCID: PMC11502925 DOI: 10.3389/fendo.2024.1412160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 06/28/2024] [Indexed: 10/29/2024] Open
Abstract
Background Obesity and frailty are prevalent geriatric conditions that share some pathophysiological mechanisms and are associated with adverse clinical outcomes. The relationship between frailty, obesity, and polymorphism remains inadequately explored. Single nucleotide polymorphisms (SNPs) offer insights into genetic predispositions that may influence the development of both frailty and obesity. Methods We aimed at investigating whether SNPs associated with frailty also play a role in obesity. Data were collected from the FRASNET cross-sectional study, which included community-dwelling older individuals residing in Milan and nearby areas. Participants were recruited through random sampling. They underwent multidimensional geriatric assessments, which included the collection of blood samples for SNP analysis. Frailty was assessed using the frailty index, and body composition was evaluated using bioelectrical impedance analysis and anthropometric measures. Results SNPs related to frailty and linked to the renin-angiotensin system (CYP11B2 rs1799998, AGT rs5051, and AGTR1 rs2131127), apoptosis pathways (CASP8 rs6747918), growth hormone signaling (GHR rs6180), inflammation (TLR4 rs5030717, CD33 rs3865444, and FN1 rs7567647), adducin (ADD3 rs3731566), and the 9p21-23 region (rs518054) were found to be associated with various measures of obesity in community-dwelling older adults. Conclusions Frailty-related SNPs contribute to obesity in community-dwelling older adults. We identified a novel association between adducin SNPs and visceral fat, which has not been previously reported. Detecting genetic predispositions to obesity and frailty early could aid in identifying individuals at risk, facilitating the adoption of preventive interventions. This represents an initial step toward promoting early intervention strategies.
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Affiliation(s)
- Sarah Damanti
- Internal Medicine Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Lorena Citterio
- Nephrology and Dialysis Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Laura Zagato
- Nephrology and Dialysis Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Elena Brioni
- Internal Medicine Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Cristiano Magnaghi
- Scientific Technical Secretariat of the Ethics Committee, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Marco Simonini
- Nephrology and Dialysis Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Rebecca De Lorenzo
- Internal Medicine Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | | | | | | | | | - Giordano Vitali
- Internal Medicine Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Manunta
- Vita-Salute San Raffaele University, Milan, Italy
- Nephrology and Dialysis Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Angelo Andrea Manfredi
- Vita-Salute San Raffaele University, Milan, Italy
- Department of Immunology, Transplantation and Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Chiara Lanzani
- Vita-Salute San Raffaele University, Milan, Italy
- Nephrology and Dialysis Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
| | - Patrizia Rovere Querini
- Internal Medicine Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
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Xia M, Li W, Lin H, Zeng H, Ma S, Wu Q, Ma H, Li X, Pan B, Gao J, Hu Y, Liu Y, Wang S, Gao X. DNA methylation age acceleration contributes to the development and prediction of non-alcoholic fatty liver disease. GeroScience 2024; 46:3525-3542. [PMID: 37605101 PMCID: PMC11226581 DOI: 10.1007/s11357-023-00903-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 08/06/2023] [Indexed: 08/23/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is prevalent in the aging society. Despite body weight reduction, the prevalence of NAFLD has been increasing with aging for unknown reasons. Here, we investigate the association of DNA methylation age acceleration, a hallmark of aging, with risk of NAFLD. Genome-wide DNA methylation profiles were measured in 95 participants who developed type 2 diabetes during 4-year follow-up, and 356 randomly sampled participants from Shanghai Changfeng Study. DNA methylation age was calculated using the Horvath's method, and liver fat content (LFC) was measured using a quantitative ultrasound method. Subjects with highest tertile of DNA methylation age acceleration (≥ 9.5 years) had significantly higher LFC (7.2% vs 3.1%, P = 0.008) but lower body fat percentage (29.7% vs 33.0%, P = 0.032) than those with lowest tertile of DNA methylation age acceleration (< 4.0 years). After adjustment for age, sex, alcohol drinking, cigarette smoking, BMI, waist circumference, and different type blood cell counts, the risk of NAFLD was still significantly increased in the highest tertile group (OR, 4.55; 95% CI, 1.06-19.61). Even in subjects with similar LFC at baseline, DNA methylation age acceleration was associated with higher increase in LFC (4.0 ± 10.7% vs 0.9 ± 9.5%, P = 0.004) after a median of 4-year follow-up. Further analysis found that 6 CpGs of Horvath age predictors were associated with longitudinal changes in LFC after multivariate adjustment and located on genes that might lead to fat redistribution from peripheral adipose to liver. Combination of the key CpG methylation related to liver fat content with conventional risk factors improves the performance for NAFLD prediction.
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Affiliation(s)
- Mingfeng Xia
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Human Phenome Institute, Fudan University, Shanghai, 201203, China
| | - Wenran Li
- CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Rd, Shanghai, 200031, China
| | - Huandong Lin
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Human Phenome Institute, Fudan University, Shanghai, 201203, China
| | - Hailuan Zeng
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Human Phenome Institute, Fudan University, Shanghai, 201203, China
| | - Shuai Ma
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Human Phenome Institute, Fudan University, Shanghai, 201203, China
| | - Qi Wu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Human Phenome Institute, Fudan University, Shanghai, 201203, China
| | - Hui Ma
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Xiaoming Li
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China
- Human Phenome Institute, Fudan University, Shanghai, 201203, China
| | - Baishen Pan
- Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Jian Gao
- Department of Nutrition, Zhongshan Hospital of Fudan University, Shanghai, 200032, China
| | - Yu Hu
- Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Yun Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Sijia Wang
- CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Rd, Shanghai, 200031, China.
- Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China.
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China.
- Human Phenome Institute, Fudan University, Shanghai, 201203, China.
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10
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Sanfeliu-Redondo D, Gibert-Ramos A, Gracia-Sancho J. Cell senescence in liver diseases: pathological mechanism and theranostic opportunity. Nat Rev Gastroenterol Hepatol 2024; 21:477-492. [PMID: 38485755 DOI: 10.1038/s41575-024-00913-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/12/2024] [Indexed: 06/30/2024]
Abstract
The liver is not oblivious to the passage of time, as ageing is a major risk factor for the development of acute and chronic liver diseases. Ageing produces alterations in all hepatic cells, affecting their phenotype and function and worsening the prognosis of liver disease. The ageing process also implies the accumulation of a cellular state characterized by a persistent proliferation arrest and a specific secretory phenotype named cellular senescence. Indeed, senescent cells have key roles in many physiological processes; however, their accumulation owing to ageing or pathological conditions contributes to the damage occurring in chronic diseases. The aim of this Review is to provide an updated description of the pathophysiological events in which hepatic senescent cells are involved and their role in liver disease progression. Finally, we discuss novel geroscience therapies that could be applied to prevent or improve liver diseases and age-mediated hepatic deregulations.
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Affiliation(s)
- David Sanfeliu-Redondo
- Liver Vascular Biology Laboratory, IDIBAPS Biomedical Research Institute - Hospital Clínic de Barcelona & CIBEREHD, Barcelona, Spain
| | - Albert Gibert-Ramos
- Liver Vascular Biology Laboratory, IDIBAPS Biomedical Research Institute - Hospital Clínic de Barcelona & CIBEREHD, Barcelona, Spain
| | - Jordi Gracia-Sancho
- Liver Vascular Biology Laboratory, IDIBAPS Biomedical Research Institute - Hospital Clínic de Barcelona & CIBEREHD, Barcelona, Spain.
- Department of Visceral Surgery and Medicine, Inselspital - University of Bern, Bern, Switzerland.
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11
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Ivo JFM, Gomes TLN, Mainardi LG, Peixoto MDRG, Costa NA, Pimentel GD. Low handgrip strength is related to elevated echogenicity in patients with chronic kidney disease: A pilot, cross-sectional and exploratory study. Rev Esp Geriatr Gerontol 2024; 59:101497. [PMID: 38795680 DOI: 10.1016/j.regg.2024.101497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 04/04/2024] [Accepted: 04/11/2024] [Indexed: 05/28/2024]
Abstract
OBJECTIVES Evaluate associations between triceps braqui muscle ultrasound measures (TB US) and handgrip strength (HGS), and the sensibility of TB US for low HGS in non-dialysis-dependent chronic kidney disease (nd-CKD) patients. PARTICIPANTS AND METHODS This pilot, cross-sectional, and exploratory study evaluated TB cross-sectional images from A-mode US and processed by FIJI-Image J to obtain muscle thickness (MT), echogenicity (EI), cross-sectional area (CSA), pennation angle (PA), and fascicle length (Lf) associating them with absolute HGS by simple and, multiple linear regression. The HGS was normalized to body mass index (BMI) and separated into low HGS (HGS/BMI≤10p according to sex and age) and adequate HGS (HGS/BMI>10p) groups. The body composition was from multifrequency bioimpedance. ROC analysis verified the TB US diagnostic accuracy to low HGS. RESULTS Were included 42 (21M/21F) adults with 65.5 (60-70) y median age, 47.22% in 3b CKD stage. The low HGS group (45.23%) showed a higher fat mass (FM), TB muscle medium head's PA, and EI than adequate HGS (p<0.05). In crude model, a pixels increase in EI was associated with a 0.452kgf HGS reduction (p=0.019); adjusted for sex, age, and FM, a one-unit increase in EI was associated with a 0.510kgf HGS reduction (p=0.011). The EI also showed moderate diagnostic accuracy (AUC=0.730; CI 95%=0.589; 0.919) to low HGS and a sensitivity of 86.9% (cutoff≥13.52 pixels). CONCLUSION In nd-CKD patients, of all measurements from US, the EI was the most associated with HGS, and the only one sensitive to low HGS diagnosis.
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Affiliation(s)
| | - Tatyanne L N Gomes
- Post-Graduation in Nutrition and Health, Faculty of Nutrition, Federal University of Goias, Goiânia, GO, Brazil
| | - Lara G Mainardi
- Post-Graduation in Nutrition and Health, Faculty of Nutrition, Federal University of Goias, Goiânia, GO, Brazil
| | | | - Nara Aline Costa
- Post-Graduation in Nutrition and Health, Faculty of Nutrition, Federal University of Goias, Goiânia, GO, Brazil
| | - Gustavo Duarte Pimentel
- Post-Graduation in Nutrition and Health, Faculty of Nutrition, Federal University of Goias, Goiânia, GO, Brazil.
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12
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Zhu Y, Hu Y, Pan Y, Li M, Niu Y, Zhang T, Sun H, Zhou S, Liu M, Zhang Y, Wu C, Ma Y, Guo Y, Wang L. Fatty infiltration in the musculoskeletal system: pathological mechanisms and clinical implications. Front Endocrinol (Lausanne) 2024; 15:1406046. [PMID: 39006365 PMCID: PMC11241459 DOI: 10.3389/fendo.2024.1406046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Accepted: 06/10/2024] [Indexed: 07/16/2024] Open
Abstract
Fatty infiltration denotes the anomalous accrual of adipocytes in non-adipose tissue, thereby generating toxic substances with the capacity to impede the ordinary physiological functions of various organs. With aging, the musculoskeletal system undergoes pronounced degenerative alterations, prompting heightened scrutiny regarding the contributory role of fatty infiltration in its pathophysiology. Several studies have demonstrated that fatty infiltration affects the normal metabolism of the musculoskeletal system, leading to substantial tissue damage. Nevertheless, a definitive and universally accepted generalization concerning the comprehensive effects of fatty infiltration on the musculoskeletal system remains elusive. As a result, this review summarizes the characteristics of different types of adipose tissue, the pathological mechanisms associated with fatty infiltration in bone, muscle, and the entirety of the musculoskeletal system, examines relevant clinical diseases, and explores potential therapeutic modalities. This review is intended to give researchers a better understanding of fatty infiltration and to contribute new ideas to the prevention and treatment of clinical musculoskeletal diseases.
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Affiliation(s)
- Yihua Zhu
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yue Hu
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yalan Pan
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Traditional Chinese Medicine (TCM) Nursing Intervention Laboratory of Chronic Disease Key Laboratory, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Muzhe Li
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yuanyuan Niu
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Tianchi Zhang
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Haitao Sun
- Department of Orthopedic Surgery, Affiliated Huishan Hospital of Xinglin College of Nantong University, Wuxi, Jiangsu, China
| | - Shijie Zhou
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Mengmin Liu
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yili Zhang
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chengjie Wu
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yong Ma
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng TCM Hospital, Yancheng, Jiangsu, China
- Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu, China
| | - Yang Guo
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Jiangsu CM Clinical Innovation Center of Degenerative Bone & Joint Disease, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu, China
| | - Lining Wang
- Laboratory of New Techniques of Restoration & Reconstruction, Institute of Traumatology & Orthopedics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
- Chinese Medicine Centre (International Collaboration between Western Sydney University and Beijing University of Chinese Medicine), Western Sydney University, Sydney, Australia
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13
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Liu M, Lu F, Feng J. Aging and homeostasis of the hypodermis in the age-related deterioration of skin function. Cell Death Dis 2024; 15:443. [PMID: 38914551 PMCID: PMC11196735 DOI: 10.1038/s41419-024-06818-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 02/01/2024] [Accepted: 06/10/2024] [Indexed: 06/26/2024]
Abstract
Adipose tissues in the hypodermis, the crucial stem cell reservoir in the skin and the endocrine organ for the maintenance of skin homeostasis undergo significant changes during skin aging. Dermal white adipose tissue (dWAT) has recently been recognized as an important organ for both non-metabolic and metabolic health in skin regeneration and rejuvenation. Defective differentiation, adipogenesis, improper adipocytokine production, and immunological dissonance dysfunction in dWAT lead to age-associated clinical changes. Here, we review age-related alterations in dWAT across levels, emphasizing the mechanisms underlying the regulation of aging. We also discuss the pathogenic changes involved in age-related fat dysfunction and the unfavorable consequences of accelerated skin aging, such as chronic inflammaging, immunosenescence, delayed wound healing, and fibrosis. Research has shown that adipose aging is an early initiation event and a potential target for extending longevity. We believe that adipose tissues play an essential role in aging and form a potential therapeutic target for the treatment of age-related skin diseases. Further research is needed to improve our understanding of this phenomenon.
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Affiliation(s)
- Meiqi Liu
- Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong, 510515, People's Republic of China
| | - Feng Lu
- Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong, 510515, People's Republic of China
| | - Jingwei Feng
- Department of Plastic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong, 510515, People's Republic of China.
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14
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Stein MJ, Fischer B, Bohmann P, Ahrens W, Berger K, Brenner H, Günther K, Harth V, Heise JK, Karch A, Klett-Tammen CJ, Koch-Gallenkamp L, Krist L, Lieb W, Meinke-Franze C, Michels KB, Mikolajczyk R, Nimptsch K, Obi N, Peters A, Pischon T, Schipf S, Schmidt B, Stang A, Thierry S, Willich SN, Wirkner K, Leitzmann MF, Sedlmeier AM. Differences in Anthropometric Measures Based on Sex, Age, and Health Status: Findings From the German National Cohort (NAKO). DEUTSCHES ARZTEBLATT INTERNATIONAL 2024; 121:207-213. [PMID: 38377337 PMCID: PMC11539873 DOI: 10.3238/arztebl.m2024.0016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 01/22/2024] [Accepted: 01/22/2024] [Indexed: 02/22/2024]
Abstract
BACKGROUND Obesity is a worldwide health problem. We conducted detailed analyses of anthropometric measures in a comprehensive, population-based, current cohort in Germany. METHODS In the German National Cohort (NAKO), we analyzed cross-sectional data on body mass index (BMI), waist and hip circumference, subcutaneous (SAT) and visceral adipose tissue (VAT) as measured by ultrasound, and body fat percentage. The data were stratified by sex, age, and self-reported physicians' diagnoses of cardiovascular diseases (CVD), metabolic diseases (MetD), cardiometabolic diseases (CMD), and cancer. RESULTS Data were available from 204 751 participants (age, 49.9 ± 12.8 years; 50.5% women). Body size measures generally increased with age. Men had a higher BMI, larger waist circumference, and more VAT than women, while women had a larger hip circumference, more SAT, and a higher body fat percentage than men. For example, the mean BMI of participants over age 60 was 28.3 kg/m2 in men and 27.6 kg/m2 in women. CVD, MetD, and CMD were associated with higher anthropometric values, while cancer was not. For example, the mean BMI was 25.3 kg/m2 in healthy women, 29.4 kg/m2 in women with CMD, and 25.4 kg/m2 in women with cancer. CONCLUSION Obesity is widespread in Germany, with notable differences between the sexes in anthro - pometric values. Obesity was more common in older participants and those with chronic diseases other than cancer. Elevated values were especially common in multimorbid individuals.
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Affiliation(s)
- Michael J. Stein
- Department of Epidemiology and Preventive Medicine, University of Regensburg
| | - Beate Fischer
- Department of Epidemiology and Preventive Medicine, University of Regensburg
| | - Patricia Bohmann
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
| | - Wolfgang Ahrens
- Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany
| | - Klaus Berger
- Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Kathrin Günther
- Leibniz Institute for Prevention Research and Epidemiology – BIPS, Bremen, Germany
| | - Volker Harth
- Institute for Occupational and Maritime Medicine Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jana-Kristin Heise
- Department for Epidemiology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - André Karch
- Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany
| | | | - Lena Koch-Gallenkamp
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Lilian Krist
- Institute of Social Medicine, Epidemiology and Health Economics, Charité—Universitätsmedizin Berlin, Berlin, Germany
| | - Wolfgang Lieb
- Institute of Epidemiology, Kiel University, Kiel, Germany
| | - Claudia Meinke-Franze
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Karin B. Michels
- Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Rafael Mikolajczyk
- Institute for Medical Epidemiology, Biometrics, and Informatics, Interdisciplinary Center for Health Sciences, Medical Faculty of the Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
| | - Katharina Nimptsch
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Nadia Obi
- Institute for Occupational and Maritime Medicine Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Annette Peters
- Institute of Epidemiology, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany
- Institute for Medical Information Processing, Biometry and Epidemiology (IBE), Medical Faculty, Ludwig-Maximilians-Universität München, Munich, Germany
- German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Biobank Technology Platform, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Sabine Schipf
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
| | - Börge Schmidt
- Institute for Medical Informatics, Biometry and Epidemiology, Essen University Hospital, University of Duisburg–Essen, Germany
| | - Andreas Stang
- Institute for Medical Informatics, Biometry and Epidemiology, Essen University Hospital, University of Duisburg–Essen, Germany
| | - Sigrid Thierry
- Institute of Epidemiology, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany
- NAKO Study Center, Department of Diagnostic and Interventional Radiology and Neuroradiology, Augsburg University Hospital, Augsburg, Germany
| | - Stefan N. Willich
- Institute of Social Medicine, Epidemiology and Health Economics, Charité—Universitätsmedizin Berlin, Berlin, Germany
| | - Kerstin Wirkner
- LIFE–Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany
| | - Michael F. Leitzmann
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
| | - Anja M. Sedlmeier
- Department of Epidemiology and Preventive Medicine, Center for Translational Oncology, University Hospital Regensburg and Bavarian Cancer Research Center (BZKF), Regensburg
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Kim JS, Lee H, Yoo A, Jeong HY, Jung CH, Ahn J, Ha TY. Gromwell ( Lithospermum erythrorhizon) Attenuates High-Fat-Induced Skeletal Muscle Wasting by Increasing Protein Synthesis and Mitochondrial Biogenesis. J Microbiol Biotechnol 2024; 34:495-505. [PMID: 38247215 PMCID: PMC11016769 DOI: 10.4014/jmb.2311.11034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 12/20/2023] [Accepted: 12/21/2023] [Indexed: 01/23/2024]
Abstract
Gromwell (Lithospermum erythrorhizon, LE) can mitigate obesity-induced skeletal muscle atrophy in C2C12 myotubes and high-fat diet (HFD)-induced obese mice. The purpose of this study was to investigate the anti-skeletal muscle atrophy effects of LE and the underlying molecular mechanism. C2C12 myotubes were pretreated with LE or shikonin, and active component of LE, for 24 h and then treated with 500 μM palmitic acid (PA) for an additional 24 h. Additionally, mice were fed a HFD for 8 weeks to induced obesity, and then fed either the same diet or a version containing 0.25% LE for 10 weeks. LE attenuated PA-induced myotubes atrophy in differentiated C2C12 myotubes. The supplementation of LE to obese mice significantly increased skeletal muscle weight, lean body mass, muscle strength, and exercise performance compared with those in the HFD group. LE supplementation not only suppressed obesity-induced skeletal muscle lipid accumulation, but also downregulated TNF-α and atrophic genes. LE increased protein synthesis in the skeletal muscle via the mTOR pathway. We observed LE induced increase of mitochondrial biogenesis and upregulation of oxidative phosphorylation related genes in the skeletal muscles. Furthermore, LE increased the expression of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha and the phosphorylation of adenosine monophosphate-activated protein kinase. Collectively, LE may be useful in ameliorating the detrimental effects of obesity-induced skeletal muscle atrophy through the increase of protein synthesis and mitochondrial biogenesis of skeletal muscle.
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Affiliation(s)
- Ji-Sun Kim
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
- Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Republic of Korea
- BK21 FOUR Institute of Precision Public Health, Interdisciplinary Program in Precision Public Health, Korea University, Seoul 02841, Republic of Korea
| | - Hyunjung Lee
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Ahyoung Yoo
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Hang Yeon Jeong
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Chang Hwa Jung
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
- Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Jiyun Ahn
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
- Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
| | - Tae-Youl Ha
- Aging and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
- Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea
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Dauchy RT, Hanifin JP, Brainard GC, Blask DE. Light: An Extrinsic Factor Influencing Animal-based Research. JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE : JAALAS 2024; 63:116-147. [PMID: 38211974 PMCID: PMC11022951 DOI: 10.30802/aalas-jaalas-23-000089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 10/26/2023] [Accepted: 10/28/2023] [Indexed: 01/13/2024]
Abstract
Light is an environmental factor that is extrinsic to animals themselves and that exerts a profound influence on the regulation of circadian, neurohormonal, metabolic, and neurobehavioral systems of all animals, including research animals. These widespread biologic effects of light are mediated by distinct photoreceptors-rods and cones that comprise the conventional visual system and melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) of the nonvisual system that interact with the rods and cones. The rods and cones of the visual system, along with the ipRGCs of the nonvisual system, are species distinct in terms of opsins and opsin concentrations and interact with one another to provide vision and regulate circadian rhythms of neurohormonal and neurobehavioral responses to light. Here, we review a brief history of lighting technologies, the nature of light and circadian rhythms, our present understanding of mammalian photoreception, and current industry practices and standards. We also consider the implications of light for vivarium measurement, production, and technological application and provide simple recommendations on artificial lighting for use by regulatory authorities, lighting manufacturers, designers, engineers, researchers, and research animal care staff that ensure best practices for optimizing animal health and well-being and, ultimately, improving scientific outcomes.
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Key Words
- blad, blue-enriched led light at daytime
- clock, circadian locomotor output kaput
- cct, correlated color temperature
- cwf, cool white fluorescent
- ign, intergeniculate nucleus
- iprgc, intrinsically photosensitive retinal ganglion cell
- hiomt, hydroxyindole-o-methyltransferase
- k, kelvin temperature
- lan, light at night
- led, light-emitting diode
- lgn, lateral geniculate nucleus
- plr, pupillary light reflex
- pot, primary optic tract
- rht, retinohypothalamic tract
- scn, suprachiasmatic nuclei
- spd, spectral power distribution.
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Affiliation(s)
- Robert T Dauchy
- Department of Structural and Cellular Biology, Laboratory of Chrono-Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, Louisiana;,
| | - John P Hanifin
- Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - George C Brainard
- Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - David E Blask
- Department of Structural and Cellular Biology, Laboratory of Chrono-Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, Louisiana
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17
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Zhao X, Jia W, Wang J, Wang S, Zheng Q, Shan T. Identification of a Candidate Gene Regulating Intramuscular Fat Content in Pigs through the Integrative Analysis of Transcriptomics and Proteomics Data. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:19154-19164. [PMID: 37987700 DOI: 10.1021/acs.jafc.3c05806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2023]
Abstract
Pork is a widely consumed source of animal protein worldwide, and the intramuscular fat (IMF) content in pork plays a crucial role in determining its quality. In this study, we sought to identify candidate genes that regulate IMF deposition in pigs. We performed tandem mass tags (TMT)-based quantitative proteomics analysis using Longissimus dorsi (LD) muscle samples obtained from eight pigs with extremely high and low IMF content among a group of 28 Duroc pigs and identified 50 differentially abundant proteins (DAPs). Additionally, we compared the proteomics data with RNA-sequencing data obtained in our previous study and identified TUSC5 as a differentially expressed gene corresponding to the relevant DAP. To investigate the potential role of TUSC5 in adipogenesis, we suppressed TUSC5 expression in mouse 3T3-L1 preadipocytes using short hairpin RNA (shRNA) and observed a significant reduction in the differentiation of 3T3-L1 cells into adipocytes, as indicated by Oil Red O staining and triglyceride content. Moreover, we observed a reduction in the expression of genes associated with adipogenesis (PPARG, CEBPA, FABP4, and FASN) following TUSC5 suppression. Through an integrative analysis of transcriptomics and proteomics data, our study identified TUSC5 as a crucial candidate gene associated with the regulation of IMF content in pigs.
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Affiliation(s)
- Xueyan Zhao
- Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China
- DELISI GROUP Co. Ltd., Weifang, Shandong 262200, China
- Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, Shandong 250100, China
| | - Wanli Jia
- Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, Shandong 250100, China
| | - Jiying Wang
- Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, Shandong 250100, China
| | - Shouwei Wang
- DELISI GROUP Co. Ltd., Weifang, Shandong 262200, China
| | - Qiankun Zheng
- DELISI GROUP Co. Ltd., Weifang, Shandong 262200, China
| | - Tizhong Shan
- Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China
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18
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Jiao Y, Sun J, Li Y, Zhao J, Shen J. Association between Adiposity and Bone Mineral Density in Adults: Insights from a National Survey Analysis. Nutrients 2023; 15:3492. [PMID: 37571429 PMCID: PMC10420642 DOI: 10.3390/nu15153492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/24/2023] [Accepted: 08/05/2023] [Indexed: 08/13/2023] Open
Abstract
Adiposity and bone mineral density (BMD) are closely associated. The aim of this research was to investigate the association between BMD and adiposity measures in adults, including gynoid percent fat (GPF), android percent fat (APF), total percent fat (TPF), visceral adipose tissue percent (VAT%), and total lean mass percent (TLM%). Participants (n = 11,615) aged 18 years and older were analyzed using data from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. Associations between BMD and adiposity measures were investigated, and potential differences based on gender and age were explored. Significant negative associations were observed among TPF, APF, GPF, VAT%, and BMD in the fully adjusted models, while TLM% and BMD were positively associated. Stratifying by age and sex, TPF, GPF, and VAT% consistently demonstrated a negative correlation with BMD. In the young adult group, a TPF of 38.2% eliminated the negative correlation between BMD and TPF. Male BMD exhibited an inverted U-shaped relationship with APF, peaking at 35.6%, while a similar pattern was observed for the middle-aged group BMD and APF, with a peak at 31.7%. This large-sample research found a significant negative association between adiposity measures and BMD, providing valuable revelations regarding the intricate connection between adiposity and bone health.
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Affiliation(s)
- Yang Jiao
- Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100730, China; (Y.J.); (J.Z.)
| | - Juan Sun
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100730, China;
| | - Yuanmeng Li
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100730, China;
| | - Junduo Zhao
- Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100730, China; (Y.J.); (J.Z.)
| | - Jianxiong Shen
- Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing 100730, China; (Y.J.); (J.Z.)
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19
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Horwitz A, Birk R. Adipose Tissue Hyperplasia and Hypertrophy in Common and Syndromic Obesity-The Case of BBS Obesity. Nutrients 2023; 15:3445. [PMID: 37571382 PMCID: PMC10421039 DOI: 10.3390/nu15153445] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 07/16/2023] [Accepted: 07/31/2023] [Indexed: 08/13/2023] Open
Abstract
Obesity is a metabolic state generated by the expansion of adipose tissue. Adipose tissue expansion depends on the interplay between hyperplasia and hypertrophy, and is mainly regulated by a complex interaction between genetics and excess energy intake. However, the genetic regulation of adipose tissue expansion is yet to be fully understood. Obesity can be divided into common multifactorial/polygenic obesity and monogenic obesity, non-syndromic and syndromic. Several genes related to obesity were found through studies of monogenic non-syndromic obesity models. However, syndromic obesity, characterized by additional features other than obesity, suggesting a more global role of the mutant genes related to the syndrome and, thus, an additional peripheral influence on the development of obesity, were hardly studied to date in this regard. This review summarizes present knowledge regarding the hyperplasia and hypertrophy of adipocytes in common obesity. Additionally, we highlight the scarce research on syndromic obesity as a model for studying adipocyte hyperplasia and hypertrophy, focusing on Bardet-Biedl syndrome (BBS). BBS obesity involves central and peripheral mechanisms, with molecular and mechanistic alternation in adipocyte hyperplasia and hypertrophy. Thus, we argue that using syndromic obesity models, such as BBS, can further advance our knowledge regarding peripheral adipocyte regulation in obesity.
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Affiliation(s)
| | - Ruth Birk
- Department of Nutrition, Faculty of Health Sciences, Ariel University, Ariel 40700, Israel;
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20
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Cho YK, Jung HN, Kim EH, Lee MJ, Park JY, Lee WJ, Kim HK, Jung CH. Association between sarcopenic obesity and poor muscle quality based on muscle quality map and abdominal computed tomography. Obesity (Silver Spring) 2023; 31:1547-1557. [PMID: 37133436 DOI: 10.1002/oby.23733] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 12/23/2022] [Accepted: 01/05/2023] [Indexed: 05/04/2023]
Abstract
OBJECTIVE This study evaluated whether sarcopenic obesity is closely associated with muscle quality using abdominal computed tomography. METHODS This cross-sectional study included 13,612 participants who underwent abdominal computed tomography. The cross-sectional area of the skeletal muscle was measured at the L3 level (total abdominal muscle area [TAMA]) and segmented into normal attenuation muscle area (NAMA, +30 to +150 Hounsfield units), low attenuation muscle area (-29 to +29 Hounsfield units), and intramuscular adipose tissue (-190 to -30 Hounsfield units). The NAMA/TAMA index was calculated by dividing NAMA by TAMA and multiplying by 100, and the lowest quartile of NAMA/TAMA index was defined as myosteatosis (<73.56 in men and <66.97 in women). Sarcopenia was defined using BMI-adjusted appendicular skeletal muscle mass. RESULTS The prevalence of myosteatosis was found to be significantly higher in participants with sarcopenic obesity (17.9% vs. 54.2%, p < 0.001) than the control group without sarcopenia or obesity. Compared with the control group, the odds ratio (95% CI) for having myosteatosis was 3.70 (2.87-4.76) for participants with sarcopenic obesity after adjusting for age, sex, smoking, drinking, exercise, hypertension, diabetes, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. CONCLUSIONS Sarcopenic obesity is significantly associated with myosteatosis, which is representative of poor muscle quality.
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Affiliation(s)
- Yun Kyung Cho
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Republic of Korea
| | - Han Na Jung
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Republic of Korea
| | - Eun Hee Kim
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Jung Lee
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Joong-Yeol Park
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Republic of Korea
| | - Woo Je Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Republic of Korea
| | - Hong-Kyu Kim
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chang Hee Jung
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Republic of Korea
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21
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Agostini D, Gervasi M, Ferrini F, Bartolacci A, Stranieri A, Piccoli G, Barbieri E, Sestili P, Patti A, Stocchi V, Donati Zeppa S. An Integrated Approach to Skeletal Muscle Health in Aging. Nutrients 2023; 15:nu15081802. [PMID: 37111021 PMCID: PMC10141535 DOI: 10.3390/nu15081802] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 03/31/2023] [Accepted: 04/04/2023] [Indexed: 04/29/2023] Open
Abstract
A decline in muscle mass and function represents one of the most problematic changes associated with aging, and has dramatic effects on autonomy and quality of life. Several factors contribute to the inexorable process of sarcopenia, such as mitochondrial and autophagy dysfunction, and the lack of regeneration capacity of satellite cells. The physiologic decline in muscle mass and in motoneuron functionality associated with aging is exacerbated by the sedentary lifestyle that accompanies elderly people. Regular physical activity is beneficial to most people, but the elderly need well-designed and carefully administered training programs that improve muscle mass and, consequently, both functional ability and quality of life. Aging also causes alteration in the gut microbiota composition associated with sarcopenia, and some advances in research have elucidated that interventions via the gut microbiota-muscle axis have the potential to ameliorate the sarcopenic phenotype. Several mechanisms are involved in vitamin D muscle atrophy protection, as demonstrated by the decreased muscular function related to vitamin D deficiency. Malnutrition, chronic inflammation, vitamin deficiencies, and an imbalance in the muscle-gut axis are just a few of the factors that can lead to sarcopenia. Supplementing the diet with antioxidants, polyunsaturated fatty acids, vitamins, probiotics, prebiotics, proteins, kefir, and short-chain fatty acids could be potential nutritional therapies against sarcopenia. Finally, a personalized integrated strategy to counteract sarcopenia and maintain the health of skeletal muscles is suggested in this review.
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Affiliation(s)
- Deborah Agostini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Marco Gervasi
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Fabio Ferrini
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Alessia Bartolacci
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Alessandro Stranieri
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Giovanni Piccoli
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Elena Barbieri
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Piero Sestili
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
| | - Antonino Patti
- Sport and Exercise Sciences Research Unit, Department of Psychology, Educational Science and Human Movement, University of Palermo, 90128 Palermo, Italy
| | - Vilberto Stocchi
- Department of Human Science for Promotion of Quality of Life, Università Telematica San Raffaele, 00166 Rome, Italy
| | - Sabrina Donati Zeppa
- Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy
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22
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Abstract
SUMMARY Over the past 30 years, there has been a dramatic increase in the use of autologous fat grafting for soft-tissue augmentation and to improve facial skin quality. Several studies have highlighted the impact of aging on adipose tissue, leading to a decrease of adipose tissue volume and preadipocyte proliferation and increase of fibrosis. Recently, there has been a rising interest in adipose tissue components, including adipose-derived stem/stromal cells (ASCs) because of their regenerative potential, including inflammation, fibrosis, and vascularization modulation. Because of their differentiation potential and paracrine function, ASCs have been largely used for fat grafting procedures, as they are described to be a key component in fat graft survival. However, many parameters as surgical procedures or adipose tissue biology could change clinical outcomes. Variation on fat grafting methods have led to numerous inconsistent clinical outcomes. Donor-to-donor variation could also be imputed to ASCs, tissue inflammatory state, or tissue origin. In this review, the authors aim to analyze (1) the parameters involved in graft survival, and (2) the effect of aging on adipose tissue components, especially ASCs, that could lead to a decrease of skin regeneration and fat graft retention. CLINICAL RELEVANCE STATEMENT This review aims to enlighten surgeons about known parameters that could play a role in fat graft survival. ASCs and their potential mechanism of action in regenerative medicine are more specifically described.
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23
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Lipoxin and glycation in SREBP signaling: Insight into diabetic cardiomyopathy and associated lipotoxicity. Prostaglandins Other Lipid Mediat 2023; 164:106698. [PMID: 36379414 DOI: 10.1016/j.prostaglandins.2022.106698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 11/15/2022]
Abstract
Diabetes and cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Diabetes increases cardiovascular risk through hyperglycemia and atherosclerosis. Chronic hyperglycemia accelerates glycation reaction, which forms advanced glycation end products (AGEs). Additionally, hyperglycemia with enhanced levels of cholesterol, native and oxidized low-density lipoproteins, free fatty acids, and oxidative stress induces lipotoxicity. Accelerated glycation and disturbed lipid metabolism are characteristic features of diabetic heart failure. SREBP signaling plays a significant role in lipid and glucose homeostasis. AGEs increase lipotoxicity in diabetic cardiomyopathy by inhibiting SREBP signaling. While anti-inflammatory lipid mediators, lipoxins resolve inflammation caused by lipotoxicity by upregulating the PPARγ expression and regulating CD36. PPARγ connects the bridge between glycation and lipoxin in SREBP signaling. A summary of treatment modalities against diabetic cardiomyopathy is given in brief. This review indicates the novel therapeutic approach in the crosstalk between glycation and lipoxin in SREBP signaling.
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24
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He Y, Su Y, Duan C, Wang S, He W, Zhang Y, An X, He M. Emerging role of aging in the progression of NAFLD to HCC. Ageing Res Rev 2023; 84:101833. [PMID: 36565959 DOI: 10.1016/j.arr.2022.101833] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 12/10/2022] [Accepted: 12/20/2022] [Indexed: 12/24/2022]
Abstract
With the aging of global population, the incidence of nonalcoholic fatty liver disease (NAFLD) has surged in recent decades. NAFLD is a multifactorial disease that follows a progressive course, ranging from simple fatty liver, nonalcoholic steatohepatitis (NASH) to liver cirrhosis and hepatocellular carcinoma (HCC). It is well established that aging induces pathological changes in liver and potentiates the occurrence and progression of NAFLD, HCC and other age-related liver diseases. Studies of senescent cells also indicate a pivotal engagement in the development of NAFLD via diverse mechanisms. Moreover, nicotinamide adenine dinucleotide (NAD+), silence information regulator protein family (sirtuins), and mechanistic target of rapamycin (mTOR) are three vital and broadly studied targets involved in aging process and NAFLD. Nevertheless, the crucial role of these aging-associated factors in aging-related NAFLD remains underestimated. Here, we reviewed the current research on the roles of aging, cellular senescence and three aging-related factors in the evolution of NAFLD to HCC, aiming at inspiring promising therapeutic targets for aging-related NAFLD and its progression.
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Affiliation(s)
- Yongyuan He
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yinghong Su
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chengcheng Duan
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Siyuan Wang
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei He
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; School of Basic Medicine, Kunming Medical University, China
| | - Yingting Zhang
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaofei An
- Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
| | - Ming He
- Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
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25
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Dauchy RT, Blask DE. Vivarium Lighting as an Important Extrinsic Factor Influencing Animal-based Research. JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE : JAALAS 2023; 62:3-25. [PMID: 36755210 PMCID: PMC9936857 DOI: 10.30802/aalas-jaalas-23-000003] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 08/26/2022] [Accepted: 09/02/2022] [Indexed: 01/22/2023]
Abstract
Light is an extrinsic factor that exerts widespread influence on the regulation of circadian, physiologic, hormonal, metabolic, and behavioral systems of all animals, including those used in research. These wide-ranging biologic effects of light are mediated by distinct photoreceptors, the melanopsin-containing intrinsically photosensitive retinal ganglion cells of the nonvisual system, which interact with the rods and cones of the conventional visual system. Here, we review the nature of light and circadian rhythms, current industry practices and standards, and our present understanding of the neurophysiology of the visual and nonvisual systems. We also consider the implications of this extrinsic factor for vivarium measurement, production, and technological application of light, and provide simple recommendations on artificial lighting for use by regulatory authorities, lighting manufacturers, designers, engineers, researchers, and research animal care staff that ensure best practices for optimizing animal health and wellbeing and, ultimately, improving scientific outcomes.
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Key Words
- blad, blue-enriched led light at daytime
- clock, circadian locomotor output kaput
- cct, correlated color temperature
- cwf, cool white fluorescent
- iprgc, intrinsically photosensitive retinal ganglion cell
- hiomt, hydroxyindole-o-methyltransferase
- lan, light at night
- led, light-emitting diode
- plr, pupillary light reflex
- scn, suprachiasmatic nuclei
- spd, spectral power distribution
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Affiliation(s)
- Robert T Dauchy
- Department of Structural and Cellular Biology, Laboratory of Chrono-Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, Louisiana
| | - David E Blask
- Department of Structural and Cellular Biology, Laboratory of Chrono-Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, Louisiana
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26
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Villareal DT. Editorial: Obesity and Accelerated Aging. J Nutr Health Aging 2023; 27:312-313. [PMID: 37248754 PMCID: PMC10349370 DOI: 10.1007/s12603-023-1922-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 04/27/2023] [Indexed: 05/31/2023]
Abstract
Through shared pathophysiologic mechanisms, obesity exacerbates the age-related decline in physical function, which leads to frailty and disability. Obesity and aging are characterized by chronic low-grade inflammation, which contributes to reduced muscle quality and protein control mechanisms as well as to diminished muscle anabolic response. Obesity causes oxidative stress and inflammation, which increases telomere shortening. Calorie excess increases ROS formation, which damages nucleus, endoplasmic reticulum, and mitochondria and promotes cellular senescence. Given the persistence of DNA damage associated with altered DNA repair proteins in obesity and aging, it is thought that inability to repair DNA may be the principal molecular event that underlies accelerated aging. Calorie restriction in combination with exercise slows biological aging by protecting against the molecular and cellular damages that occur in obesity and aging. Promising approaches such as Time Restricted Eating, Mediterranean Diet, and Senolytics need further investigation.
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Affiliation(s)
- D T Villareal
- Dennis T. Villareal, MD, Baylor College of Medicine, Michael E DeBakey VA Medical Center, 2002 Holcombe Ave, Houston, TX 77030, USA,
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27
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Aldahhan RA, Motawei KH, Al-Hariri MT. Lipotoxicity-related sarcopenia: a review. J Med Life 2022; 15:1334-1339. [PMID: 36567835 PMCID: PMC9762358 DOI: 10.25122/jml-2022-0157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 07/27/2022] [Indexed: 12/27/2022] Open
Abstract
A body of literature supports the postulation that a persistent lipid metabolic imbalance causes lipotoxicity, "an abnormal fat storage in the peripheral organs". Hence, lipotoxicity could somewhat explain the process of sarcopenia, an aging-related, gradual, and involuntary decline in skeletal muscle strength and mass associated with several health complications. This review focuses on the recent mechanisms underlying lipotoxicity-related sarcopenia. A vicious cycle occurs between sarcopenia and ectopic fat storage via a complex interplay of mitochondrial dysfunction, pro-inflammatory cytokine production, oxidative stress, collagen deposition, extracellular matrix remodeling, and life habits. The repercussions of lipotoxicity exacerbation of sarcopenia can include increased disability, morbidity, and mortality. This suggests that appropriate lipotoxicity management should be considered the primary target for the prevention and/or treatment of chronic musculoskeletal and other aging-related disorders. Further advanced research is needed to understand the molecular details of lipotoxicity and its consequences for sarcopenia and sarcopenia-related comorbidities.
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Affiliation(s)
| | - Kamaluddin Hasan Motawei
- Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammed Taha Al-Hariri
- Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia,Corresponding Author: Mohammed Taha Al-Hariri, Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. E-mail:
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28
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Zamboni M, Mazzali G, Brunelli A, Saatchi T, Urbani S, Giani A, Rossi AP, Zoico E, Fantin F. The Role of Crosstalk between Adipose Cells and Myocytes in the Pathogenesis of Sarcopenic Obesity in the Elderly. Cells 2022; 11:3361. [PMID: 36359757 PMCID: PMC9655977 DOI: 10.3390/cells11213361] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/08/2022] [Accepted: 10/14/2022] [Indexed: 11/15/2023] Open
Abstract
As a result of aging, body composition changes, with a decline in muscle mass and an increase in adipose tissue (AT), which reallocates from subcutaneous to visceral depots and stores ectopically in the liver, heart and muscles. Furthermore, with aging, muscle and AT, both of which have recognized endocrine activity, become dysfunctional and contribute, in the case of positive energy balance, to the development of sarcopenic obesity (SO). SO is defined as the co-existence of excess adiposity and low muscle mass and function, and its prevalence increases with age. SO is strongly associated with greater morbidity and mortality. The pathogenesis of SO is complex and multifactorial. This review focuses mainly on the role of crosstalk between age-related dysfunctional adipose and muscle cells as one of the mechanisms leading to SO. A better understanding of this mechanisms may be useful for development of prevention strategies and treatments aimed at reducing the occurrence of SO.
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Affiliation(s)
- Mauro Zamboni
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Gloria Mazzali
- Geriatrics Division, Department of Medicine, University of Verona, 37126 Verona, Italy
| | - Anna Brunelli
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Tanaz Saatchi
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Silvia Urbani
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Anna Giani
- Geriatrics Division, Department of Surgery, Dentistry, Pediatric and Gynecology, Healthy Aging Center, University of Verona, 37126 Verona, Italy
| | - Andrea P. Rossi
- Geriatrics Division, Department of Medicine, AULSS2, Ospedale Ca’Foncello, 31100 Treviso, Italy
| | - Elena Zoico
- Geriatrics Division, Department of Medicine, University of Verona, 37126 Verona, Italy
| | - Francesco Fantin
- Geriatrics Division, Department of Medicine, University of Verona, 37126 Verona, Italy
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Yue B, Wang H, Cai X, Wang J, Chai Z, Peng W, Shu S, Fu C, Zhong J. Adipose-Secreted Exosomes and Their Pathophysiologic Effects on Skeletal Muscle. Int J Mol Sci 2022; 23:12411. [PMID: 36293266 PMCID: PMC9604254 DOI: 10.3390/ijms232012411] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 10/07/2022] [Accepted: 10/14/2022] [Indexed: 04/30/2024] Open
Abstract
Due to its prominent secretory activity, adipose tissue (AT) is now considered a major player in the crosstalk between organs, especially with skeletal muscle. In which, exosomes are effective carriers for the intercellular material transfer of a wide range of molecules that can influence a series of physiological and pathological processes in recipient cells. Considering their underlying roles, the regulatory mechanisms of adipose-secreted exosomes and their cellular crosstalk with skeletal muscle have received great attention in the field. In this review, we describe what is currently known of adipose-secreted exosomes, as well as their applications in skeletal muscle pathophysiology.
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Affiliation(s)
- Binglin Yue
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu 610225, China
| | - Hui Wang
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu 610225, China
| | - Xin Cai
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu 610225, China
| | - Jiabo Wang
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu 610225, China
| | - Zhixin Chai
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu 610225, China
| | - Wei Peng
- Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining 810016, China
| | - Shi Shu
- Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining 810016, China
| | - Changqi Fu
- Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining 810016, China
| | - Jincheng Zhong
- Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Sichuan Province and Ministry of Education, Southwest Minzu University, Chengdu 610225, China
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Wang G, Song A, Bae M, Wang QA. Adipose Tissue Plasticity in Aging. Compr Physiol 2022; 12:4119-4132. [PMID: 36214190 DOI: 10.1002/cphy.c220005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
As a dynamic endocrine organ, white adipose tissue (WAT) stores lipids and plays a critical role in maintaining whole-body energy homeostasis and insulin sensitivity. A large group of the population over 65 years old suffer from increased WAT mass, especially in the visceral location. Visceral adiposity accelerates aging through promoting age-associated chronic conditions, significantly shortening life expectancy. Unlike WAT, brown adipose tissue (BAT) functions as an effective energy sink that burns and disposes of excess lipids and glucose upon activation of thermogenesis. Unfortunately, the thermogenic activity of BAT declines during aging. New appreciation of cellular and functional remodeling of WAT and BAT during aging has emerged in recent years. Efforts are underway to explore the potential underlying mechanisms behind these age-associated alterations in WAT and BAT and the impact of these alterations on whole-body metabolism. Lastly, it is intriguing to translate our knowledge obtained from animal models to the clinic to prevent and treat age-associated metabolic disorders. © 2022 American Physiological Society. Compr Physiol 12: 4119-4132, 2022.
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Affiliation(s)
- Guan Wang
- Department of Molecular & Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Medical Center, Duarte, California, USA
| | - Anying Song
- Department of Molecular & Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Medical Center, Duarte, California, USA
| | - Marie Bae
- Department of Molecular & Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Medical Center, Duarte, California, USA
| | - Qiong A Wang
- Department of Molecular & Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope Medical Center, Duarte, California, USA.,Comprehensive Cancer Center, Beckman Research Institute, City of Hope Medical Center, Duarte, California, USA
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Ni S, Jia M, Wang X, Hong Y, Zhao X, Zhang L, Ru Y, Yang F, Zhu S. Associations of eating speed with fat distribution and body shape vary in different age groups and obesity status. Nutr Metab (Lond) 2022; 19:63. [PMID: 36100862 PMCID: PMC9469611 DOI: 10.1186/s12986-022-00698-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 09/01/2022] [Indexed: 11/30/2022] Open
Abstract
Background Eating speed has been reported to be associated with energy intake, body weight, waist circumference (WC), and total body fat. However, no study has explored the association between eating speed and body fat distribution, especially its difference among different age or body mass index (BMI) groups. Methods 4770 participants aged 18–80 years were recruited from the baseline survey of the Lanxi Cohort Study. They were categorized into three groups according to meal duration. Linear regression analyses were performed among all participants and separately by age group and obesity status to evaluate the associations of WC and total and regional fat mass percentages (FM%) with eating speed. Results After adjusting for confounding factors, eating slowly was significantly related to lower WC, lower total, trunk, and android FM%, lower android-to-gynoid fat mass ratio, and higher leg and gynoid FM%. After stratification by age or obesity status, the associations were especially prominent among participants aged 18–44 years or those with BMI < 24 kg/m2. No significant trends were found for participants aged 65–80 years or those who were overweight/obese. Conclusions Eating slowly is closely related with better fat distribution among Chinese adults, especially for those aged 18–44 years and those with BMI < 24 kg/m2. If confirmed prospectively, it might be a potential efficient approach to improve fat distribution. Supplementary Information The online version contains supplementary material available at 10.1186/s12986-022-00698-w.
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Oh S, Kim HM, Batsukh S, Sun HJ, Kim T, Kang D, Son KH, Byun K. High-Intensity Focused Ultrasound Induces Adipogenesis via Control of Cilia in Adipose-Derived Stem Cells in Subcutaneous Adipose Tissue. Int J Mol Sci 2022; 23:ijms23168866. [PMID: 36012125 PMCID: PMC9408610 DOI: 10.3390/ijms23168866] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 07/30/2022] [Accepted: 08/07/2022] [Indexed: 11/16/2022] Open
Abstract
During skin aging, the volume of subcutaneous adipose tissue (sWAT) and the adipogenesis potential of adipose-derived stem cells (ASCs) decrease. It is known that the shortening of cilia length by pro-inflammatory cytokines is related to the decreased adipogenic differentiation of ASCs via increase in Wnt5a/β-catenin. High-intensity focused ultrasound (HIFU) is known to upregulate heat shock proteins (HSP), which decrease levels of pro-inflammatory cytokines. In this study, we evaluated whether HIFU modulates the cilia of ASCs by upregulating HSP70 and decreasing inflammatory cytokines. HIFU was applied at 0.2 J to rat skin, which was harvested at 1, 3, 7, and 28 days. All results for HIFU-applied animals were compared with control animals that were not treated. HIFU increased expression of HSP70 and decreased expression of NF-κB, IL-6, and TNF-α in sWAT. HIFU decreased the expression of cilia disassembly-related factors (AurA and HDAC9) in ASCs. Furthermore, HIFU increased the expression of cilia assembly-related factors (KIF3A and IFT88), decreased that of WNT5A/β-catenin, and increased that of the adipogenesis markers PPARγ and CEBPα in sWAT. HIFU increased the number of adipocytes in the sWAT and the thickness of sWAT. In conclusion, HIFU could selectively increase sWAT levels by modulating the cilia of ASCs and be used for skin rejuvenation.
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Affiliation(s)
- Seyeon Oh
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine, Incheon 21999, Korea
| | - Hyoung Moon Kim
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine, Incheon 21999, Korea
- Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea
| | - Sosorburam Batsukh
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine, Incheon 21999, Korea
- Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea
| | | | | | | | - Kuk Hui Son
- Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea
- Correspondence: (K.H.S.); (K.B.); Tel.: +82-32-460-3666 (K.H.S.); +82-32-899-6511 (K.B.)
| | - Kyunghee Byun
- Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine, Incheon 21999, Korea
- Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea
- Correspondence: (K.H.S.); (K.B.); Tel.: +82-32-460-3666 (K.H.S.); +82-32-899-6511 (K.B.)
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Abstract
Obesity is a complex, multifactorial, and relapsing disease whose prevalence has tripled during the last decades and whose incidence is expected to further increase. For these reasons, obesity is considered as a real pandemic, deeply burdening the global health-care systems. From a pathophysiological standpoint obesity is the result of a chronic-positive energy balance which in turn leads to an excessive accumulation of lipids, not only within the adipose organ, but also in different cytotypes, a phenomenon leading to lipotoxicity that deeply compromises several cellular and organs functions. Obesity is therefore associated with over 200 medical complications, including insulin resistance and type 2 diabetes mellitus (T2DM) and represents the fifth leading cause of death worldwide. In this review, we describe the main pathophysiological mechanisms linking obesity-induced adipose organ dysfunction to insulin resistance and T2DM.
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Garg T, Chu LC, Zimmerman SL, Weiss CR, FCIRSE MDFSIR, Fishman EK, Azadi JR. Prevalence of Hepatic Steatosis in Adults Presenting to the Emergency Department Identified by Unenhanced Chest CT. Curr Probl Diagn Radiol 2022; 52:35-40. [DOI: 10.1067/j.cpradiol.2022.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 07/27/2022] [Indexed: 11/22/2022]
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Ishaq A, Tchkonia T, Kirkland JL, Siervo M, Saretzki G. Palmitate induces DNA damage and senescence in human adipocytes in vitro that can be alleviated by oleic acid but not inorganic nitrate. Exp Gerontol 2022; 163:111798. [PMID: 35390489 PMCID: PMC9214712 DOI: 10.1016/j.exger.2022.111798] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/28/2022] [Accepted: 03/31/2022] [Indexed: 11/22/2022]
Abstract
Hypertrophy in white adipose tissue (WAT) can result in sustained systemic inflammation, hyperlipidaemia, insulin resistance, and onset of senescence in adipocytes. Inflammation and hypertrophy can be induced in vitro using palmitic acid (PA). WAT adipocytes have innately low β-oxidation capacity, while inorganic nitrate can promote a beiging phenotype, with promotion of β-oxidation when cells are exposed to nitrate during differentiation. We hypothesized that treatment of human adipocytes with PA in vitro can induce senescence, which might be attenuated by nitrate treatment through stimulation of β-oxidation to remove accumulated lipids. Differentiated subcutaneous and omental adipocytes were treated with PA and nitrate and senescence markers were analyzed. PA induced DNA damage and increased p16INK4a levels in both human subcutaneous and omental adipocytes in vitro. However, lipid accumulation and lipid droplet size increased after PA treatment only in subcutaneous adipocytes. Thus, hypertrophy and senescence seem not to be causally associated. Contrary to our expectations, subsequent treatment of PA-induced adipocytes with nitrate did not attenuate PA-induced lipid accumulation or senescence. Instead, we found a significantly beneficial effect of oleic acid (OA) on human subcutaneous adipocytes when applied together with PA, which reduced the DNA damage caused by PA treatment.
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Affiliation(s)
- Abbas Ishaq
- Biosciences Institute, Campus for Ageing and Vitality, Newcastle upon Tyne, UK
| | - Tamara Tchkonia
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, United States of America
| | - James L Kirkland
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, United States of America
| | - Mario Siervo
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK; School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK
| | - Gabriele Saretzki
- Biosciences Institute, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
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36
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Freytag L, Alfertshofer MG, Frank K, Moellhoff N, Helm S, Redaelli A, Voropai D, Hernandez CA, Green JB, Cotofana S. Understanding Facial Aging Through Facial Biomechanics. Facial Plast Surg Clin North Am 2022; 30:125-133. [DOI: 10.1016/j.fsc.2022.01.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Xie H, Liu X, Zhou Q, Huang T, Zhang L, Gao J, Wang Y, Liu Y, Yan T, Zhang S, Wang CY. DNA Methylation Modulates Aging Process in Adipocytes. Aging Dis 2022; 13:433-446. [PMID: 35371604 PMCID: PMC8947842 DOI: 10.14336/ad.2021.0904] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 09/04/2021] [Indexed: 11/17/2022] Open
Abstract
Aging has been recognized to be a highly complex biological health problem with a high risk of chronic diseases, including type 2 diabetes, atherosclerosis, chronic bronchitis or emphysema, cancer and Alzheimer's disease. Particularly, age-related turnover in adipose tissue is a major contributor to metabolic syndromes and shortened lifespan. Adipocytes undergo senescence in early stage, which results in adipose tissue metabolic dysfunction, redistribution, and inflammation. The well-established association between DNA methylation (DNAm) and aging has been observed in the past few decades. Indeed, age-related alteration in DNAm is highly tissue-specific. This review intends to summarize the advancements how DNAm changes coupled with aging process in adipose tissue, by which DNAm regulates cellular senescence, metabolic function, adipokine secretion and beiging process in adipocytes. Elucidation of the effect of DNAm on adipose aging would have great potential to the development of epigenetic therapeutic strategies against aging-related diseases in clinical settings.
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Affiliation(s)
- Hao Xie
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Xin Liu
- Department of Interventional Radiology, Renmin Hospital of Wuhan University, Wuhan, China.
| | - Qing Zhou
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Teng Huang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Lu Zhang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Jia Gao
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Yuhan Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Yanjun Liu
- The Center for Obesity and Metabolic Health, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Sichuan, China.,The Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu & The affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.
| | - Tong Yan
- The Center for Obesity and Metabolic Health, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Sichuan, China.
| | - Shu Zhang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Correspondence should be addressed to: Drs. Cong-Yi Wang () or Shu Zhang (), the Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cong-Yi Wang
- The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Correspondence should be addressed to: Drs. Cong-Yi Wang () or Shu Zhang (), the Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Kim M, Oh JH, Won CW. Sex-Specific Differences in Lower Body Fat Distribution and Association with Physical Performance among Healthy Community-Dwelling Older Adults: A Pilot Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19074201. [PMID: 35409882 PMCID: PMC8998698 DOI: 10.3390/ijerph19074201] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Revised: 03/29/2022] [Accepted: 03/30/2022] [Indexed: 12/02/2022]
Abstract
This study aims to examine sex-specific differences in body composition and lower extremity fat distribution and their association with physical performance among healthy older adults. The pilot study comprises 40 subjects (20 men and 20 women) matched by age and body mass index. The participants undergo dual-energy X-ray absorptiometry, magnetic resonance imaging, and proton magnetic resonance spectroscopy (1H-MRS) to assess body composition and lower extremity fat distribution. 1H-MRS is used to measure the extramyocellular lipid (EMCL) and intramyocellular lipid (IMCL) contents of the lower leg muscles (soleus and tibialis anterior) at the maximum circumference of the calf after overnight fasting. The tibialis anterior IMCL, as assessed by 1H-MRS, is negatively associated with the five-times sit-to-stand test scores (rs = 0.518, p = 0.023) in men, while the soleus IMCL content is negatively associated with the timed up-and-go test scores (rs = 0.472, p = 0.048) in women. However, the soleus EMCL content is positively associated with the five-times sit-to-stand test scores (rs = −0.488, p = 0.040) in women, but this association is not statistically significant in men. This study shows an inverse correlation between IMCL content and physical performance in healthy older individuals and lower leg muscle-specific IMCL based on sex differences. Furthermore, our results suggest that greater EMCL content in the soleus and calf subcutaneous fat might affect physical performance positively in women but not men.
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Affiliation(s)
- Miji Kim
- Department of Biomedical Science and Technology, College of Medicine, East-West Medical Research Institute, Kyung Hee University, Seoul 02447, Korea
- Correspondence: (M.K.); (C.W.W.); Tel.: +82-2-958-2840 (M.K.); +82-2-958-8700 (C.W.W.)
| | - Jang-Hoon Oh
- Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul 02447, Korea;
| | - Chang Won Won
- Department of Family Medicine, College of Medicine, Kyung Hee University, Seoul 02447, Korea
- Correspondence: (M.K.); (C.W.W.); Tel.: +82-2-958-2840 (M.K.); +82-2-958-8700 (C.W.W.)
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Park S. Biochemical, structural and physical changes in aging human skin, and their relationship. Biogerontology 2022; 23:275-288. [PMID: 35292918 DOI: 10.1007/s10522-022-09959-w] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 02/25/2022] [Indexed: 11/02/2022]
Abstract
Skin is the largest organ of the human body, having the purpose of regulating temperature, protecting us from microbes or mechanical shocks, and allowing the sensations from touch. It is generally accepted that aging induces profound changes in the skin's biochemical, structural and physical properties, which can lead to impaired biological functions and/or diverse diseases. So far, the effects of aging on these skin properties have been well documented. However, very few studies have focused exclusively on the relationship among these critical properties in the aging process, which is this review's primary focus. Many in vivo, ex vivo, and in vitro techniques have been previously used to characterize these properties of the skin. This review aims to provide a comprehensive overview on the effects of aging on the changes in biochemical, structural, and physical properties, and explore the potential mechanisms of skin with the relation between these properties. First, we review different or contradictory results of aging-related changes in representative parameters of each property, including the interpretations of the findings. Next, we discuss the need for a standardized method to characterize aging-related changes in these properties, to improve the way of defining age-property relationship. Moreover, potential mechanisms based on the previous results are explored by linking the biochemical, structural, and physical properties. Finally, the need to study changes of various functional properties in the separate skin layers is addressed. This review can help understand the underlying mechanism of aging-related alterations, to improve the evaluation of the aging process and guide effective treatment strategies for aging-related diseases.
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Affiliation(s)
- Seungman Park
- Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, 21218, USA. .,Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
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Benítez R, Núñez Y, Ayuso M, Isabel B, Fernández-Barroso MA, De Mercado E, Gómez-Izquierdo E, García-Casco JM, López-Bote C, Óvilo C. Changes in Biceps femoris Transcriptome along Growth in Iberian Pigs Fed Different Energy Sources and Comparative Analysis with Duroc Breed. Animals (Basel) 2021; 11:ani11123505. [PMID: 34944282 PMCID: PMC8697974 DOI: 10.3390/ani11123505] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/26/2021] [Accepted: 12/06/2021] [Indexed: 12/19/2022] Open
Abstract
Simple Summary The genetic mechanisms that regulate biological processes, such as skeletal muscle development and growth, or intramuscular fat deposition, have attracted great interest, given their impact on production traits and meat quality. In this sense, a comparison of the transcriptome of skeletal muscle between phenotypically different pig breeds, or along growth, could be useful to improve the understanding of the molecular processes underlying the differences in muscle metabolism and phenotypic traits, potentially driving the identification of causal genes, regulators and metabolic pathways involved in their variability. Abstract This experiment was conducted to investigate the effects of developmental stage, breed, and diet energy source on the genome-wide expression, meat quality traits, and tissue composition of biceps femoris muscle in growing pure Iberian and Duroc pigs. The study comprised 59 Iberian (IB) and 19 Duroc (DU) animals, who started the treatment at an average live weight (LW) of 19.9 kg. The animals were kept under identical management conditions and fed two diets with different energy sources (6% high oleic sunflower oil or carbohydrates). Twenty-nine IB animals were slaughtered after seven days of treatment at an average LW of 24.1 kg, and 30 IB animals plus all the DU animals were slaughtered after 47 days at an average LW of 50.7 kg. The main factors affecting the muscle transcriptome were age, with 1832 differentially expressed genes (DEGs), and breed (1055 DEGs), while the effect of diet on the transcriptome was very small. The results indicated transcriptome changes along time in Iberian animals, being especially related to growth and tissue development, extracellular matrix (ECM) composition, and cytoskeleton organization, with DEGs affecting relevant functions and biological pathways, such as myogenesis. The breed also affected functions related to muscle development and cytoskeleton organization, as well as functions related to solute transport and lipid and carbohydrate metabolism. Taking into account the results of the two main comparisons (age and breed effects), we can postulate that the Iberian breed is more precocious than the Duroc breed, regarding myogenesis and muscle development, in the studied growing stage.
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Affiliation(s)
- Rita Benítez
- Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), 28040 Madrid, Spain; (R.B.); (Y.N.); (M.A.F.-B.); (J.M.G.-C.)
| | - Yolanda Núñez
- Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), 28040 Madrid, Spain; (R.B.); (Y.N.); (M.A.F.-B.); (J.M.G.-C.)
| | - Miriam Ayuso
- Department of Veterinary Sciences, Faculty of Biomedical, Pharmaceutical and Veterinary Sciences, University of Antwerp, B-2610 Wilrijk, Belgium;
| | - Beatriz Isabel
- Departamento de Producción Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain; (B.I.); (C.L.-B.)
| | - Miguel A. Fernández-Barroso
- Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), 28040 Madrid, Spain; (R.B.); (Y.N.); (M.A.F.-B.); (J.M.G.-C.)
| | - Eduardo De Mercado
- Centro de Pruebas de Porcino ITACYL, Hontalbilla, 40353 Segovia, Spain; (E.D.M.); (E.G.-I.)
| | - Emilio Gómez-Izquierdo
- Centro de Pruebas de Porcino ITACYL, Hontalbilla, 40353 Segovia, Spain; (E.D.M.); (E.G.-I.)
| | - Juan M. García-Casco
- Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), 28040 Madrid, Spain; (R.B.); (Y.N.); (M.A.F.-B.); (J.M.G.-C.)
| | - Clemente López-Bote
- Departamento de Producción Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain; (B.I.); (C.L.-B.)
| | - Cristina Óvilo
- Departamento de Mejora Genética Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CSIC), 28040 Madrid, Spain; (R.B.); (Y.N.); (M.A.F.-B.); (J.M.G.-C.)
- Correspondence: ; Tel.: +34-91-3471492
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Queen NJ, Deng H, Huang W, Mo X, Wilkins RK, Zhu T, Wu X, Cao L. Environmental Enrichment Mitigates Age-Related Metabolic Decline and Lewis Lung Carcinoma Growth in Aged Female Mice. Cancer Prev Res (Phila) 2021; 14:1075-1088. [PMID: 34535449 PMCID: PMC8639669 DOI: 10.1158/1940-6207.capr-21-0085] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/05/2021] [Accepted: 08/31/2021] [Indexed: 11/16/2022]
Abstract
Aging is a complex physiological process that leads to the progressive decline of metabolic and immune function, among other biological mechanisms. As global life expectancy increases, it is important to understand determinants of healthy aging-including environmental and genetic factors-and thus slow the onset or progression of age-related disease. Environmental enrichment (EE) is a housing environment wherein laboratory animals engage with complex physical and social stimulation. EE is a prime model to understand environmental influences on aging dynamics, as it confers an antiobesity and anticancer phenotype that has been implicated in healthy aging and health span extension. Although EE is frequently used to study malignancies in young mice, fewer studies characterize EE-cancer outcomes in older mice. Here, we used young (3-month-old) and aged (14-month-old) female C57BL/6 mice to determine whether EE would be able to mitigate age-related deficiencies in metabolic function and thus alter Lewis lung carcinoma (LLC) growth. Overall, EE improved metabolic function, resulting in reduced fat mass, increased lean mass, and improved glycemic processing; many of these effects were stronger in the aged cohort than in the young cohort, indicating an age-driven effect on metabolic responses. In the aged-EE cohort, subcutaneously implanted LLC tumor growth was inhibited and tumors exhibited alterations in various markers of apoptosis, proliferation, angiogenesis, inflammation, and malignancy. These results validate EE as an anticancer model in aged mice and underscore the importance of understanding environmental influences on cancer malignancy in aged populations. PREVENTION RELEVANCE: Environmental enrichment (EE) serves as a model of complex physical and social stimulation. This study validates EE as an anticancer intervention paradigm in aged mice and underscores the importance of understanding environmental influences on cancer malignancy in aged populations.
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Affiliation(s)
- Nicholas J Queen
- Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, Ohio
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Hong Deng
- Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, Ohio
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
- Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
- Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Wei Huang
- Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, Ohio
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Xiaokui Mo
- Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, Ohio
| | - Ryan K Wilkins
- Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, Ohio
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Tao Zhu
- Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Xiaoyu Wu
- Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Lei Cao
- Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, Ohio.
- The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
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42
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Low E, Alimohammadiha G, Smith LA, Costello LF, Przyborski SA, von Zglinicki T, Miwa S. How good is the evidence that cellular senescence causes skin ageing? Ageing Res Rev 2021; 71:101456. [PMID: 34487917 PMCID: PMC8524668 DOI: 10.1016/j.arr.2021.101456] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 08/25/2021] [Accepted: 08/31/2021] [Indexed: 12/11/2022]
Abstract
Skin is the largest organ of the body with important protective functions, which become compromised with time due to both intrinsic and extrinsic ageing processes. Cellular senescence is the primary ageing process at cell level, associated with loss of proliferative capacity, mitochondrial dysfunction and significantly altered patterns of expression and secretion of bioactive molecules. Intervention experiments have proven cell senescence as a relevant cause of ageing in many organs. In case of skin, accumulation of senescence in all major compartments with ageing is well documented and might be responsible for most, if not all, the molecular changes observed during ageing. Incorporation of senescent cells into in-vitro skin models (specifically 3D full thickness models) recapitulates changes typically associated with skin ageing. However, crucial evidence is still missing. A beneficial effect of senescent cell ablation on skin ageing has so far only been shown following rather unspecific interventions or in transgenic mouse models. We conclude that evidence for cellular senescence as a relevant cause of intrinsic skin ageing is highly suggestive but not yet completely conclusive.
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Affiliation(s)
- Evon Low
- Ageing Biology Laboratories, Newcastle University Biosciences Institute, Newcastle University, Newcastle upon Tyne NE4 5PL, UK
| | - Ghazaleh Alimohammadiha
- Ageing Biology Laboratories, Newcastle University Biosciences Institute, Newcastle University, Newcastle upon Tyne NE4 5PL, UK
| | - Lucy A Smith
- Department of Biosciences, Durham University, South Road, Durham DH1 3LE, UK
| | - Lydia F Costello
- Department of Biosciences, Durham University, South Road, Durham DH1 3LE, UK
| | - Stefan A Przyborski
- Department of Biosciences, Durham University, South Road, Durham DH1 3LE, UK
| | - Thomas von Zglinicki
- Ageing Biology Laboratories, Newcastle University Biosciences Institute, Newcastle University, Newcastle upon Tyne NE4 5PL, UK.
| | - Satomi Miwa
- Ageing Biology Laboratories, Newcastle University Biosciences Institute, Newcastle University, Newcastle upon Tyne NE4 5PL, UK
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43
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The Critical Role of Oxidative Stress in Sarcopenic Obesity. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:4493817. [PMID: 34676021 PMCID: PMC8526202 DOI: 10.1155/2021/4493817] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 09/22/2021] [Indexed: 12/11/2022]
Abstract
Sarcopenic obesity (SO) is a combination of obesity and sarcopenia that primarily develops in older people. Patients with SO have high fat mass, low muscle mass, low muscle strength, and low physical function. SO relates to metabolic syndrome and an increased risk of morbimortality. The prevalence of SO varies because of lacking consensus criteria regarding its definition and the methodological difficulty in diagnosing sarcopenia and obesity. SO includes systemic alterations such as insulin resistance, increased proinflammatory cytokines, age-associated hormonal changes, and decreased physical activity at pathophysiological levels. Interestingly, these alterations are influenced by oxidative stress, which is a critical factor in altering muscle function and the generation of metabolic dysfunctions. Thus, oxidative stress in SO alters muscle mass, the signaling pathways that control it, satellite cell functions, and mitochondrial and endoplasmic reticulum activities. Considering this background, our objectives in this review are to describe SO as a highly prevalent condition and look at the role of oxidative stress in SO pathophysiology.
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44
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Kim DH, Bang E, Ha S, Jung HJ, Choi YJ, Yu BP, Chung HY. Organ-differential Roles of Akt/FoxOs Axis as a Key Metabolic Modulator during Aging. Aging Dis 2021; 12:1713-1728. [PMID: 34631216 PMCID: PMC8460295 DOI: 10.14336/ad.2021.0225] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 02/25/2021] [Indexed: 12/11/2022] Open
Abstract
FoxOs and their post-translational modification by phosphorylation, acetylation, and methylation can affect epigenetic modifications and promote the expression of downstream target genes. Therefore, they ultimately affect cellular and biological functions during aging or occurrence of age-related diseases including cancer, diabetes, and kidney diseases. As known for its key role in aging, FoxOs play various biological roles in the aging process by regulating reactive oxygen species, lipid accumulation, and inflammation. FoxOs regulated by PI3K/Akt pathway modulate the expression of various target genes encoding MnSOD, catalases, PPARγ, and IL-1β during aging, which are associated with age-related diseases. This review highlights the age-dependent differential regulatory mechanism of Akt/FoxOs axis in metabolic and non-metabolic organs. We demonstrated that age-dependent suppression of Akt increases the activity of FoxOs (Akt/FoxOs axis upregulation) in metabolic organs such as liver and muscle. This Akt/FoxOs axis could be modulated and reversed by antiaging paradigm calorie restriction (CR). In contrast, hyperinsulinemia-mediated PI3K/Akt activation inhibited FoxOs activity (Akt/FoxOs axis downregulation) leading to decrease of antioxidant genes expression in non-metabolic organs such as kidneys and lungs during aging. These phenomena are reversed by CR. The results of studies on the process of aging and CR indicate that the Akt/FoxOs axis plays a critical role in regulating metabolic homeostasis, redox stress, and inflammation in various organs during aging process. The benefical actions of CR on the Akt/FoxOs axis in metabolic and non-metabolic organs provide further insights into the molecular mechanisms of organ-differential roles of Akt/FoxOs axis during aging.
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Affiliation(s)
- Dae Hyun Kim
- 1Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-gu, Busan 46241, Korea
| | - EunJin Bang
- 1Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-gu, Busan 46241, Korea
| | - Sugyeong Ha
- 1Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-gu, Busan 46241, Korea
| | - Hee Jin Jung
- 1Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-gu, Busan 46241, Korea
| | - Yeon Ja Choi
- 2Department of Biopharmaceutical Engineering, Division of Chemistry and Biotechnology, Dongguk University, Gyeongju 38066, Korea
| | - Byung Pal Yu
- 3Department of Physiology, The University of Texas Health Science Center at San Antonio, TX 78229, USA
| | - Hae Young Chung
- 1Department of Pharmacy, College of Pharmacy, Pusan National University, Gumjung-gu, Busan 46241, Korea
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45
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Colleluori G, Villareal DT. Aging, obesity, sarcopenia and the effect of diet and exercise intervention. Exp Gerontol 2021; 155:111561. [PMID: 34562568 DOI: 10.1016/j.exger.2021.111561] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 09/14/2021] [Accepted: 09/15/2021] [Indexed: 12/25/2022]
Abstract
The number of adults 65 years and older is increasing worldwide and will represent the 20% of the population by 2030. Half of them will suffer from obesity. The decline in muscle mass and strength, known as sarcopenia, is very common among older adults with obesity (sarcopenic obesity). Sarcopenic obesity is strongly associated with frailty, cardiometabolic dysfunction, physical disability, and mortality. Increasing efforts have been hence made to identify effective strategies able to promote healthy aging and curb the obesity pandemic. Among these, lifestyle interventions consisting of diet and exercise protocols have been extensively explored. Importantly, diet-induced weight loss is associated with fat, muscle, and bone mass losses, and may further exacerbate age-related sarcopenia and frailty outcomes in older adults. Successful approaches to induce fat mass loss while preserving lean and bone mass are critical to reduce the aging- and obesity-related physical and metabolic complications and at the same time ameliorate frailty. In this review article, we discuss the most recent evidence on the age-related alterations in adipose tissue and muscle health and on the effect of calorie restriction and exercise approaches for older adults with obesity and sarcopenia, emphasizing the existing gaps in the literature that need further investigation.
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Affiliation(s)
- Georgia Colleluori
- Department of Experimental and Clinical Medicine, Center for the Study of Obesity, Marche Polytechnic University, Ancona, Italy; Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center, Houston, TX, USA
| | - Dennis T Villareal
- Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine, Houston, TX, USA; Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center, Houston, TX, USA.
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46
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Alqahtani SA, Schattenberg JM. NAFLD in the Elderly. Clin Interv Aging 2021; 16:1633-1649. [PMID: 34548787 PMCID: PMC8448161 DOI: 10.2147/cia.s295524] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/12/2021] [Indexed: 12/25/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent disease globally. Current estimates are that 24% of the adult population, thus, one billion individuals worldwide, are affected. Interestingly, the prevalence of fatty liver seems to peak between 40─50 years of age in males and 60─69 years in females, often slightly decreasing in older (>70 years) cohorts. Furthermore, several risk factors for NAFLD development, such as hypertension, diabetes, hyperlipidemia, and obesity are higher in older adults. The diagnosis and management strategies in older adults are sometimes challenging, and certain age-specific factors have to be taken into account by healthcare professionals. In this review, we provide an overview of considerations relevant to the management and diagnosis of NAFLD in older adults (age >65 years) and discuss the types of pharmacological interventions available for the management of non-alcoholic steatohepatitis (NASH) in the aging population.
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Affiliation(s)
- Saleh A Alqahtani
- Liver Transplantation Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.,Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Jörn M Schattenberg
- Metabolic Liver Research Program, I. Department of Medicine, University Medical Center, Mainz, Germany
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47
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Le Pelletier L, Mantecon M, Gorwood J, Auclair M, Foresti R, Motterlini R, Laforge M, Atlan M, Fève B, Capeau J, Lagathu C, Bereziat V. Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction. eLife 2021; 10:62635. [PMID: 34544550 PMCID: PMC8526089 DOI: 10.7554/elife.62635] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 09/03/2021] [Indexed: 01/09/2023] Open
Abstract
Aging is associated with central fat redistribution and insulin resistance. To identify age-related adipose features, we evaluated the senescence and adipogenic potential of adipose-derived stromal cells (ASCs) from abdominal subcutaneous fat obtained from healthy normal-weight young (<25 years) or older women (>60 years). Increased cell passages of young-donor ASCs (in vitro aging) resulted in senescence but not oxidative stress. ASC-derived adipocytes presented impaired adipogenesis but no early mitochondrial dysfunction. Conversely, aged-donor ASCs at early passages displayed oxidative stress and mild senescence. ASC-derived adipocytes exhibited oxidative stress, and early mitochondrial dysfunction but adipogenesis was preserved. In vitro aging of aged-donor ASCs resulted in further increased senescence, mitochondrial dysfunction, oxidative stress, and severe adipocyte dysfunction. When in vitro aged young-donor ASCs were treated with metformin, no alteration was alleviated. Conversely, metformin treatment of aged-donor ASCs decreased oxidative stress and mitochondrial dysfunction resulting in decreased senescence. Metformin's prevention of oxidative stress and of the resulting senescence improved the cells' adipogenic capacity and insulin sensitivity. This effect was mediated by the activation of AMP-activated protein kinase as revealed by its specific inhibition and activation. Overall, aging ASC-derived adipocytes presented impaired adipogenesis and insulin sensitivity. Targeting stress-induced senescence of ASCs with metformin may improve age-related adipose tissue dysfunction.
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Affiliation(s)
- Laura Le Pelletier
- Sorbonne Université, Inserm UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), RHU CARMMA, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Matthieu Mantecon
- Sorbonne Université, Inserm UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), RHU CARMMA, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Jennifer Gorwood
- Sorbonne Université, Inserm UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), RHU CARMMA, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Martine Auclair
- Sorbonne Université, Inserm UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), RHU CARMMA, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | | | | | - Mireille Laforge
- CNRS, INSERM UMRS_1124, Faculté des sciences fondamentales et biomédicales, Université de Paris, Paris, France
| | - Michael Atlan
- AP-HP, Tenon Hospital, Department of Plastic Surgery, Paris, France
| | - Bruno Fève
- AP-HP, Saint-Antoine Hospital, Department of Endocrinology, PRISIS, Paris, France
| | - Jacqueline Capeau
- Sorbonne Université, Inserm UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), RHU CARMMA, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Claire Lagathu
- Sorbonne Université, Inserm UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), RHU CARMMA, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Veronique Bereziat
- Sorbonne Université, Inserm UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), RHU CARMMA, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
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48
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Age and Sex: Impact on adipose tissue metabolism and inflammation. Mech Ageing Dev 2021; 199:111563. [PMID: 34474078 DOI: 10.1016/j.mad.2021.111563] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 08/19/2021] [Accepted: 08/26/2021] [Indexed: 02/08/2023]
Abstract
Age associated chronic inflammation is a major contributor to diseases with advancing age. Adipose tissue function is at the nexus of processes contributing to age-related metabolic disease and mediating longevity. Hormonal fluctuations in aging potentially regulate age-associated visceral adiposity and metabolic dysfunction. Visceral adiposity in aging is linked to aberrant adipogenesis, insulin resistance, lipotoxicity and altered adipokine secretion. Age-related inflammatory phenomena depict sex differences in macrophage polarization, changes in T and B cell numbers, and types of dendritic cells. Sex differences are also observed in adipose tissue remodeling and cellular senescence suggesting a role for sex steroid hormones in the regulation of the adipose tissue microenvironment. It is crucial to investigate sex differences in aging clinical outcomes to identify and better understand physiology in at-risk individuals. Early interventions aimed at targets involved in adipose tissue adipogenesis, remodeling and inflammation in aging could facilitate a profound impact on health span and overcome age-related functional decline.
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49
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Loo EXL, Zhang Y, Yap QV, Yu G, Soh SE, Loy SL, Lau HX, Chan SY, Shek LPC, Luo ZC, Yap FKP, Tan KH, Chong YS, Zhang J, Eriksson JG. Comparative epidemiology of gestational diabetes in ethnic Chinese from Shanghai birth cohort and growing up in Singapore towards healthy outcomes cohort. BMC Pregnancy Childbirth 2021; 21:566. [PMID: 34407778 PMCID: PMC8375167 DOI: 10.1186/s12884-021-04036-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 08/02/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) has been associated with adverse health outcomes for mothers and offspring. Prevalence of GDM differs by country/region due to ethnicity, lifestyle and diagnostic criteria. We compared GDM rates and risk factors in two Asian cohorts using the 1999 WHO and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. METHODS The Shanghai Birth Cohort (SBC) and the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort are prospective birth cohorts. Information on sociodemographic characteristics and medical history were collected from interviewer-administered questionnaires. Participants underwent a 2-h 75-g oral glucose tolerance test at 24-28 weeks gestation. Logistic regressions were performed. RESULTS Using the 1999 WHO criteria, the prevalence of GDM was higher in GUSTO (20.8%) compared to SBC (16.6%) (p = 0.046). Family history of hypertension and alcohol consumption were associated with higher odds of GDM in SBC than in GUSTO cohort while obesity was associated with higher odds of GDM in GUSTO. Using the IADPSG criteria, the prevalence of GDM was 14.3% in SBC versus 12.0% in GUSTO. A history of GDM was associated with higher odds of GDM in GUSTO than in SBC, while being overweight, alcohol consumption and family history of diabetes were associated with higher odds of GDM in SBC. CONCLUSIONS We observed several differential risk factors of GDM among ethnic Chinese women living in Shanghai and Singapore. These findings might be due to heterogeneity of GDM reflected in diagnostic criteria as well as in unmeasured genetic, lifestyle and environmental factors.
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Affiliation(s)
- Evelyn Xiu Ling Loo
- Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore, 117609, Singapore. .,Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
| | - Yuqing Zhang
- Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,School of Public Health, Shanghai Jiao Tong University, Shanghai, China
| | - Qai Ven Yap
- Department of Biostatistics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Guoqi Yu
- Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shu E Soh
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - See Ling Loy
- Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore, 117609, Singapore.,Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore.,Duke-NUS Medical School, Singapore, Singapore
| | - Hui Xing Lau
- Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore, 117609, Singapore
| | - Shiao-Yng Chan
- Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore, 117609, Singapore.,Department of Obstetrics & Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
| | - Lynette Pei-Chi Shek
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Zhong-Cheng Luo
- Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, M5G 1X5, Canada
| | - Fabian Kok Peng Yap
- Duke-NUS Medical School, Singapore, Singapore.,Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore.,Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Kok Hian Tan
- Department of Maternal Fetal Medicine, KK Women's and Children's Hospital, Singapore, Singapore
| | - Yap Seng Chong
- Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore, 117609, Singapore.,Department of Obstetrics & Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore
| | - Jun Zhang
- Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,School of Public Health, Guilin Medical College, Guilin, Guangxi, China
| | - Johan Gunnar Eriksson
- Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore, 117609, Singapore.,Department of Obstetrics & Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.,Folkhälsan Research Center, Helsinki, Finland.,Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
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50
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De Ycaza AEE, Søndergaard E, Morgan-Bathke M, Leon BGC, Lytle KA, Ramos P, Kirkland JL, Tchkonia T, Jensen MD. Senescent cells in human adipose tissue: A cross-sectional study. Obesity (Silver Spring) 2021; 29:1320-1327. [PMID: 34114359 PMCID: PMC8859802 DOI: 10.1002/oby.23202] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 03/29/2021] [Accepted: 04/20/2021] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Adipose tissue (AT) senescence is associated with AT dysfunction in rodents, but little is known about human AT senescence. The study goal was to define the distribution of senescent cells in two subcutaneous depots and understand relationships with adiposity and inflammation. METHODS Sixty-three volunteers (48 females) underwent abdominal and femoral subcutaneous fat biopsies. Fat cell size, senescent cells using senescence-associated β-galactosidase staining per 100 nucleated cells (percentage), and mRNA expression of four cytokines were measured. RESULTS There was a larger proportion of senescent cells in femoral than abdominal subcutaneous AT (mean difference 1.6% [95% CI: 0.98%-2.3%], p < 0.001), and the percentage of femoral AT senescent cells was greater in women than men (median 3.9% vs. 2.1%, p < 0.01). There was a positive correlation between senescence and fat cell size in abdominal (rs = 0.44, p < 0.001) and femoral (rs = 0.35, p = 0.007) AT depots. Abdominal AT tumor necrosis factor alpha (rs = 0.49, p < 0.01) and interleukin-1β (rs = 0.44, p = 0.01) expression was positively correlated with abdominal, but not femoral, AT senescence. CONCLUSIONS In human subcutaneous AT, there are more senescent cells in femoral than abdominal depots; abdominal AT senescent cells are more associated with inflammatory signals than femoral AT senescent cells.
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Affiliation(s)
- Ana Elena Espinosa De Ycaza
- Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
- Facultad de Medicina, Universidad de Panamá, Panama City, Republic of Panama
- Panamanian Institute of Biological Research, Panama City, Republic of Panama
| | - Esben Søndergaard
- Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
- Steno Diabetes Center Aarhus, Aarhus, Denmark
- The Danish Diabetes Academy, Odense, Denmark
| | - Maria Morgan-Bathke
- Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
- Nutrition and Dietetics, Viterbo University, La Crosse, WI, USA
| | - Barbara Gisella Carranza Leon
- Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
- Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kelli A. Lytle
- Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
| | - Paola Ramos
- Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
| | - James L. Kirkland
- Robert & Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA
| | - Tamar Tchkonia
- Robert & Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA
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