Minireviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Mar 26, 2015; 7(2): 512-520
Published online Mar 26, 2015. doi: 10.4252/wjsc.v7.i2.512
Molecular mechanism of extrinsic factors affecting anti-aging of stem cells
Tzyy Yue Wong, Mairim Alexandra Solis, Ying-Hui Chen, Lynn Ling-Huei Huang
Tzyy Yue Wong, Mairim Alexandra Solis, Ying-Hui Chen, Lynn Ling-Huei Huang, Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan
Lynn Ling-Huei Huang, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan
Author contributions: Wong TY, Solis MA, Chen YH and Huang LLH wrote this paper.
Supported by A grant from the National Science Council, Taiwan.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lynn Ling-Huei Huang, PhD, Institute of Biotechnology, College of Bioscience and Biotechnology, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan. lynn@mail.ncku.edu.tw
Telephone: +886-6-2757575 Fax: +886-6-2080165
Received: August 25, 2014
Peer-review started: August 25, 2014
Revised: October 2, 2014
Accepted: November 17, 2014
Article in press: November 19, 2014
Published online: March 26, 2015
Abstract

Scientific evidence suggests that stem cells possess the anti-aging ability to self-renew and maintain differentiation potentials, and quiescent state. The objective of this review is to discuss the micro-environment where stem cells reside in vivo, the secreted factors to which stem cells are exposed, the hypoxic environment, and intracellular factors including genome stability, mitochondria integrity, epigenetic regulators, calorie restrictions, nutrients, and vitamin D. Secreted tumor growth factor-β and fibroblast growth factor-2 are reported to play a role in stem cell quiescence. Extracellular matrices may interact with caveolin-1, the lipid raft on cell membrane to regulate quiescence. N-cadherin, the adhesive protein on niche cells provides support for stem cells. The hypoxic micro-environment turns on hypoxia-inducible factor-1 to prevent mesenchymal stem cells aging through p16 and p21 down-regulation. Mitochondria express glucosephosphate isomerase to undergo glycolysis and prevent cellular aging. Epigenetic regulators such as p300, protein inhibitors of activated Stats and H19 help maintain stem cell quiescence. In addition, calorie restriction may lead to secretion of paracrines cyclic ADP-ribose by intestinal niche cells, which help maintain intestinal stem cells. In conclusion, it is crucial to understand the anti-aging phenomena of stem cells at the molecular level so that the key to solving the aging mystery may be unlocked.

Keywords: Stem cells, Anti-aging, Quiescence, Micro-environment

Core tip: This review approaches anti-aging from aspect of stem cells. Stem cells may interact directly with their extracellular surroundings through caveolin-1, a lipid raft protein, to carry out and maintain stem cell functions. Mechanisms through hypoxia-inducible factor-1, glycolysis, and epigenetic regulators such as p300, protein inhibitors of activated Stats and H19 play crucial role in stem cell quiescence, and anti-aging regulations. Conversely, genomic instability such as DNA double-strand-breaks modulate cellular aging through the mammalian target of rapamycin pathway, which may lead to decreased lifespan.