Abstract Up to now numerous studies in the field of gerontology have been published. Nevertheless, a well-known food restriction remains the most reliable and efficient way of lifespan extension. Physical activity is also a well-documented anti-aging intervention being especially efficient in slowing down the age-associated decline of skeletal muscle mass. In this review we focus on the molecular mechanisms of the effect of physical exercise on muscle tissues. We also discuss the possibilities of pharmacological extension of this effect to the rest of the tissues. During the exercise, the level of ATP decreases triggering activation of AMP-dependent protein kinase (AMPK). This kinase stimulates antioxidant potential of the cells and their mitochondrial respiratory capacity. The exercise also induces mild oxidative stress, which, in turn, mediates the stimulation via hormetic response. Furthermore, during the exercise cells generate activators of mammalian target of rapamycin (mTOR). The intracellular ATP level increases during the rest periods between exercises thus promoting mTOR activation. Therefore, regular exercise intermittently activates anti-oxidant defenses and mitochondrial biogenesis (via AMPK and the hormetic response) of the muscle tissue, as well as its proliferative potential (via mTOR), which, in turn, impedes the age-dependent muscle atrophy. Thus, the intermittent treatment with activators of (i) AMPK combined with the inducers of hormetic response and of (ii) mTOR might partly mimic the effects of physical exercise. Importantly, pharmacological activation of AMPK takes place in the absence of ATP level decrease. The use of uncouplers of respiration and oxidative phosphorylation at the phase of AMPK activation could also prevent negative consequences of the cellular hyper-energization. It is believed that the decline of both antioxidant and proliferative potentials of the cells causes the age-dependent decline of multiple tissues, rather than only the muscular one. We argue that the approach above is applicable for the majority of tissues in an organism.

中文翻译：

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操纵细胞能量学以减缓组织和器官的衰老

摘要 迄今为止，已经发表了大量老年学领域的研究。尽管如此，众所周知的食物限制仍然是延长寿命的最可靠和最有效的方式。体育锻炼也是一种有据可查的抗衰老干预措施，在减缓与年龄相关的骨骼肌质量下降方面特别有效。在这篇综述中，我们关注体育锻炼对肌肉组织影响的分子机制。我们还讨论了将这种效应药理学扩展到其他组织的可能性。在运动过程中，ATP 水平降低，触发 AMP 依赖性蛋白激酶 (AMPK) 的激活。这种激酶刺激细胞的抗氧化潜力及其线粒体呼吸能力。运动还会引起轻度氧化应激，反过来，通过激素反应介导刺激。此外，在运动过程中，细胞会产生哺乳动物雷帕霉素靶标 (mTOR) 的激活剂。细胞内 ATP 水平在运动之间的休息期间增加，从而促进 mTOR 激活。因此，定期运动会间歇性地激活肌肉组织的抗氧化防御和线粒体生物合成（通过 AMPK 和激素反应），以及其增殖潜力（通过 mTOR），从而阻止与年龄相关的肌肉萎缩。因此，用 (i) AMPK 激活剂与兴奋反应和 (ii) mTOR 诱导剂相结合的间歇治疗可能部分模拟体育锻炼的效果。重要的是，AMPK 的药理学激活发生在 ATP 水平不降低的情况下。在 AMPK 激活阶段使用呼吸解偶联剂和氧化磷酸化也可以防止细胞过度激发的负面后果。据信，细胞的抗氧化和增殖潜力的下降会导致多种组织的年龄依赖性下降，而不仅仅是肌肉组织。我们认为上述方法适用于生物体中的大多数组织。