This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial
atrophy of gastric glands, impaired mucosal defense (reduced
bicarbonate and
prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as
ethanol,
aspirin and other non-steroidal anti-inflammatory drugs (
NSAIDs), impaired healing of injury and reduced therapeutic efficacy of
ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired
oxygen delivery cause
hypoxia, which leads to activation of the early growth response-1 (egr-1)
transcription factor. Activation of egr-1, in turn, upregulates the
dual specificity phosphatase,
phosphatase and
tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic
caspase-3 and
caspase-9 and reduced expression of the anti-apoptosis
protein,
survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of
survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced
telomerase activity, increase in replicative cellular senescence, and reduced expression of
vascular endothelial growth factor and
importin-α-a nuclear transport
protein essential for transport of
transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older patients have much greater risk of
gastroduodenal ulcers and gastrointestinal complications (e.g.,
NSAIDs-induced gastric injury) than younger patients; and (3) increased susceptibility of aging gastric mucosa to injury can be potentially reduced or reversed pharmacologically.