运动通过调节SCFAs延缓衰老及其作用机制的研究进展

Research progress on the anti-aging effect of exercise-mediated SCFAs regulation and mechanisms

短链脂肪酸(SCFAs)作为肠道菌群的代谢产物,其水平失衡与衰老以及增龄相关疾病的发生发展关系密切。本文通过归纳、总结近年运动与老年人产SCFAs菌群相关的研究,系统论述运动对SCFAs的影响,以及SCFAs介导运动延缓衰老可能的作用机制。结果显示:运动能优化老年人肠道菌群组成,使产SCFAs菌群占比增加,促进SCFAs产生;运动调控SCFAs延缓衰老的分子机制可能涉及炎症反应、糖脂代谢及细胞自噬等多个方面。(1)炎症状态缓解:SCFAs激活GPR41/GPR43或HDAC抑制NF-κB通路,降低炎症因子水平,缓解炎性衰老。(2)改善糖脂代谢:SCFAs一方面通过GPR41/GPR43受体促进PYY、GLP-1和瘦素释放,加速血糖被骨骼肌或脂肪组织摄取利用;另一方面介导AMPK通路抑制肝脏糖异生,同时通过AMPK通路上调脂肪组织UCP-1/UCP-2等产热蛋白或ATGL等脂解蛋白表达,促进脂肪氧化与分解。(3)影响细胞自噬:SCFAs可经由AMPK/mTOR或PI3K/Akt/mTOR通路调控细胞自噬,改善衰老相关疾病病程。本文以SCFAs为切入点,对运动调控SCFAs表达进而延缓衰老的生物学机制进行梳理、分析,以期为运动促进老年人健康及其作用机制研究提供全新的参考与理论依据。

Short-chain fatty acids(SCFAs)are the main metabolites produced by anaerobic fermentation of SCFA producers among gut microbiota.SCFA imbalance exhibits a strong relationship with aging and an increased incidence of age-related diseases.This review summarizes the existing knowledge on physical exercise and SCFAs.The effect of exercise on SCFA producers in elderly adults and the mechanism of anti-aging through improving SCFA production by exercise are systematically described.The results demonstrate that exercise can optimize gut microbiota composition in elderly adults and promote SCFA production by increasing the proportion of SCFA producers.The mechanism of exercise-mediated SCFA upregulation may involve inflammation,glycolipid metabolism,and autophagy,leading to the following conclusions.(1)Inflammation alleviation:SCFAs can activate GPR41/GPR43 or HDAC to inhibit NF-kB pathway,which reduces the expression of inflammatory factors.(2)Improving glucose and lipid metabolism:SCFAs can modulate the release of PYY,GLP-1 and leptin through GPR41/GPR43 receptors to accelerate glucose uptake in skeletal muscle and adipose tissue and activate AMPK pathway to inhibit gluconeogenesis simultaneously.SCFAs also promote lipid oxidation and lipolysis by upregulating the expression of thermogenic proteins in adipose tissue through AMPK pathway,such as UCP-1/UCP-2 or lipolytic proteins(ATGL).(3)Influence on autophagy:SCFAs can regulate autophagy via AMPK/mTOR or PI3K/Akt/mTOR pathway to induce age-related diseases.This review summarizes the biological mechanism of exercise-mediated SCFA upregulation in anti-aging,hoping to provide a new reference and theoretical basis for further studies on health promotion by exercise in the elderly and the underlying mechanisms.