Sestrins are evolutionarily conserved mediators of exercise benefits
Sestrins are evolutionarily conserved mediators of exercise benefits
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DOI：
10.1038/s41467-019-13442-5
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发表时间：
2020-01-13
影响因子：
16.6
通讯作者：
Lee, Jun Hee
中科院分区：
文献类型：
--
作者：
Kim, Myungjin;Sujkowski, Alyson;Lee, Jun Hee
运动是治疗与年龄相关的活动能力下降和代谢失调的最有效的干预措施之一。虽然长期耐力运动可以促进胰岛素敏感性并扩大呼吸能力，但调节运动代谢益处的遗传成分和途径仍然难以捉摸。在这里，我们表明，Sestrins，一个进化保守的运动诱导蛋白家族，是运动益处的关键介质。在果蝇和小鼠模型中，Sestrins的基因消融阻止生物体获得运动的代谢益处，并通过训练提高其耐力。相反，Sestrin上调模拟运动的分子和生理效应，表明它可能是运动代谢的主要效应子。在Sestrin对运动的反应中调节的各种靶点中，AKT和PGC1 α对于Sestrin在延长耐力方面的作用至关重要。这些结果表明，Sestrin是一个关键的整合因素，驱动慢性运动的新陈代谢和身体耐力的好处。运动改善代谢健康和身体状况，特别是对老年人的健康很重要。在这里，作者确定运动诱导的Sestrins蛋白是代谢适应运动的关键介质，并通过AKT和PGC1a轴增加耐力。
Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1 alpha are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance.Exercise improves metabolic health and physical condition, particularly important for health in aged individuals. Here, the authors identify that Sestrins, proteins induced by exercise, are key mediators of the metabolic adaptation to exercise and increase endurance through the AKT and PGC1a axes.