Increased susceptibility of aging gastric mucosa to injury and delayed healing: Clinical implications

Table 2 Structural, functional and biochemical abnormalities of aging gastric mucosa

Partial atrophy of gastric glands and their replacement with connective tissue

Degenerative changes in parietal and chief cells

↓ Sensory innervation and abolished hyperemic response to mild and moderate irritants

↓ Bicarbonate and prostaglandin generation and secretion

↓ Mucosal blood flow (by > 60%) and profound hypoxia of all mucosal cells

↑ Expression and transcriptional activity of early growth response-1→ ↑ PTEN and ↓ survivin (anti-apoptosis protein) → ↑ apoptosis

Other abnormalities include:

↓ Telomerase activity, cellular senescence, increased lipid peroxidation, impaired hypoxia sensor in endothelial (and epithelial?) cells

↑ Reactive oxygen species

Downregulated or mutated Klotho protein and dysregulated mitochondrial-nuclear communication

↓ Importin-α expression in endothelial cells of gastric mucosa → ↓activation and ↓expression of vascular endothelial growth factor (VEGF), which is a pro-angiogenic factor and protects gastric endothelial cells; imbalance between VEGF and endostatin

↓ Expression of nerve growth factor in gastric mucosal endothelial cells → reduced endothelial cell viability, impaired angiogenesis and gastric ulcer healing

Revised from World J Gastroenterol 2014[29] and updated based on our previous publications[24-29].