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| 1 | Increased susceptibility of aging gastric mucosa to injury:The mechanisms and clinical implications显示文摘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. | Andrzej S Tarnawski Amrita Ahluwalia Michael K Jones | 2014 | World Journal of Gastroenterology2014，20，16： | 16 |
| 2 | Current understanding of the mechanisms of stem cell aging显示文摘Remarkable progress has taken place in the research of stem cells during the past 30 years.General perceptions,experimental and clinical evidences pinpoint the fact that functional decline of tissue often coincides with aging-related diseases.Stem cell aging plays a fundamental role in the dysregulation of tissue function,maintenance,and repairing.This review specifically focuses on the current findings and emerging concepts of hematopoietic stem cell aging and its mechanisms. | ZHU XuDong LI TangLiang JU ZhenYu | 2016 | Science Foundation in China2016，24，3： | 0 |
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