Increased susceptibility of aging gastric mucosa to injury: the mechanisms and clinical implications
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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.
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Increased sensitivity to stress and PCD is observed in aging gastric mucosa.
“Finally, increased sensitivity to stress and PCD is observed in aging gastric mucosa, and rodent studies implicate caspase-3 activation (Tarnawski et al., 2014).”
From Programmed cell death in aging (2015) · cites this paper as Tarnawski et al., 2014
Rodent studies implicate caspase-3 activation in aging gastric mucosa.
“Finally, increased sensitivity to stress and PCD is observed in aging gastric mucosa, and rodent studies implicate caspase-3 activation (Tarnawski et al., 2014).”
From Programmed cell death in aging (2015) · cites this paper as Tarnawski et al., 2014
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- Authors
- Tarnawski, A. S.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Tarnawski, Andrzej S
- ORCID
- Tarnawski, Andrzej S
- Venue
- World Journal of Gastroenterology
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2014
- Volume
- 20
- Issue
- 16
- Pages
- 4467
- ISSN
- 1007-9327 (ISSN-L)
- PMC
- PMC4000484
- OpenAlex
- W2138901859
- Cited by
- 70
- References
- 72
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 4
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Gastroenterology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- American College of Gastroenterology
- American Gastroenterological Association
- American Society for Investigative Pathology
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal Bleeding Diagnosis and Treatment
- Keywords
- gastric mucosal injury, atrophic gastritis, mucosal protection, EGR1, PTEN, caspase-3, caspase-9, survivin, apoptosis, telomerase, cellular senescence, vascular endothelial growth factor, importin alpha, NSAID-induced gastropathy, peptic ulcer, gastric mucosal blood flow
- MeSH terms
- Age Factors, Aging, Animals, Gastric Mucosa, Gastrointestinal Agents, Humans, Risk Factors, Stomach Diseases, Signal Transduction, Treatment Outcome
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