Increased susceptibility of aging gastric mucosa to injury: The mechanisms and clinical implications

Table 1 Structural, functional and biochemical abnormalities of aging gastric mucosa

Partial atrophy of gastric glands in the basal one-third of the mucosa and their replacement with connective tissue

Degenerative changes in parietal and chief cells and accumulation of disorganized collagen fibrils in connective tissue immediately adjacent to capillary blood vessels. The latter most likely interferes with transport of oxygen and nutrients

Reduced sensory innervation and abolished hyperemic response to mild and moderate irritants

Reduced bicarbonate and prostaglandin generation and secretion

Reduced (by 60%) mucosal blood flow and profound hypoxia of epithelial cells

Increased expression of egr-1 and its transcriptional activity-most likely responsible for activation of thePTENgene

Increased expression of PTEN mRNA and protein (pro-apoptosis protein) and reduced expression of survivin (anti-apoptosis protein); this imbalance results in increased apoptosis

Increased apoptosis

Other abnormalities: reduced telomerase activity, cellular senescence, increased lipid peroxidation, impaired hypoxia sensor in endothelial (and epithelial?) cells, increased reactive oxygen species, downregulated or mutated Klotho protein in some submucosal neural elements, and dysregulated mitochondrial-nuclear communication

Decreased importin-αexpression in endothelial cells of gastric mucosa leading to reduced activation and expression of vascular endothelial growth factor, which is a pro-angiogenic factor and protects gastric endothelial cells

All the above changes underlie increased susceptibility of aging gastric mucosa to injury by a variety of factors including aspirin and other non-steroidal anti-inflammatory drugs, ethanol, ischemia/reperfusion and others, and these changes most likely impair injury healing. PTEN: Phosphatase and tensin homologue deleted on chromosome ten.