Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
Cells. 2021 Sep 19;10(9):2479. doi: 10.3390/cells10092479.
Chronic exercise is widely recognized as an important contributor to healthspan in humans and in diverse animal models. Recently, we have demonstrated that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits in flies and mice. Knockout of Sestrins prevents exercise adaptations to endurance and flight in , and similarly prevents benefits to endurance and metabolism in exercising mice. In contrast, overexpression of dSestrin in muscle mimics several of the molecular and physiological adaptations characteristic of endurance exercise. Here, we extend those observations to examine the impact of dSestrin on preserving speed and increasing lysosomal activity. We find that dSestrin is a critical factor driving exercise adaptations to climbing speed, but is not absolutely required for exercise to increase lysosomal activity in . The role of Sestrin in increasing speed during chronic exercise requires both the TORC2/AKT axis and the PGC1α homolog , while dSestrin requires interactions with TORC1 to cell-autonomously increase lysosomal activity. These results highlight the conserved role of Sestrins as key factors that drive diverse physiological adaptations conferred by chronic exercise.
慢性运动被广泛认为是人类和多种动物模型中健康寿命的重要贡献者。最近，我们已经证明，Sestrins 是一组进化上保守的运动诱导蛋白，是运动对果蝇和小鼠有益的关键介质。Sestrins 的敲除阻止了运动对耐力和飞行的适应，同样也阻止了运动对耐力和代谢的益处。相比之下，肌肉中超表达 dSestrin 可模拟耐力运动的几个分子和生理适应特征。在这里，我们扩展了这些观察结果，以研究 dSestrin 对保持速度和增加溶酶体活性的影响。我们发现，dSestrin 是驱动运动对攀爬速度适应的关键因素，但对于运动增加 中的溶酶体活性并非绝对必需。Sestrin 在慢性运动中增加速度的作用需要 TORC2/AKT 轴和 PGC1α 同源物，而 dSestrin 需要与 TORC1 相互作用，以细胞自主性方式增加溶酶体活性。这些结果突出了 Sestrins 作为关键因素的保守作用，这些因素驱动了慢性运动带来的多种生理适应。
