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

Abstract

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.

The ageing gastrointestinal tract

“…The latter has been found to be associated with low body weight andareducedintakeofmicronutrientsincludingfibre, folate, and vitamins B2 and B6, and volunteers with small intestinal bacterial overgrowth more frequently reported loose stool/diarrhoea than those without (22 vs. 11%) [26]. Elderly patients are recognized to be prone to the development of chronic gastritis, gastroduodenal ulcers, and bleeding as a consequence of NSAID use and Helicobacter pylori infection [22,27,28]. The fundamental process of angiogenesis (formation of new blood vessels, which is essential for healing of ulcers) is impaired in the ageing gastric mucosa [29].…”

Adenosine A2A-receptor agonist polydeoxyribonucleotide promotes gastric ulcer healing in Mongolian gerbils

“…The balance between Bax and Bcl-2 determines the mitochondrial response to apoptotic stimuli (Upadhyay et al 2003). An imbalance between proapoptotic and anti-apoptotic mediators initiates apoptosis and enhances susceptibility to gastric mucosa injury (Tarnawski et al 2014).…”

Efecto gastroprotector y capacidad antioxidante del extracto acuoso de las vainas de Caesalpinia spinosa ‘tara’, en animales de experimentación

“…En la figura 2 se puede observar el precipitado gelatinoso al realizar las observaciones macroscópicas de los estó-magos tratados con dosis de 800 mg/kg y en menor cantidad a la dosis de 400 mg/kg. La hidrotalcita, un antiácido que contiene aluminio y magnesio similar al hidroflat, se ha comprobado que ejerce una acción protectora sobre la mucosa gástrica dañada en ratas y reduce significativamente la lesión inducida por etanol y AINEs mediante la preservación de las células endoteliales de los vasos sanguí-neos de la mucosa y las células progenitoras epiteliales (27,28) . Lo señalado anteriormente difiere con los resultados obtenidos en este estudio, ya que el hidroflat a la dosis usada no logró la protección mucogástrica deseada en comparación al extracto de tara.…”