Manipulating Cellular Energetics to Slow Aging of Tissues and Organsстатья
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Дата последнего поиска статьи во внешних источниках: 17 июля 2020 г.
Аннотация:Up to now numerous studies in the field of gerontology have beenpublished. Nevertheless, a well-known food restriction remains the most reliable andefficient way of lifespan extension. Physical activity is also a well-documented antiaging intervention being especially efficient in slowing down the age-associated declineof skeletal muscle mass. In this review we focus on the molecular mechanisms of theeffect of physical exercise on muscle tissues. We also discuss the possibilities ofpharmacological 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 theirmitochondrial respiratory capacity. The exercise also induces mild oxidative stress,which, in turn, mediates the stimulation via hormetic response. Furthermore, during theexercise cells generate activators of mammalian target of rapamycin (mTOR). Theintracellular ATP level increases during the rest periods between exercises thuspromoting mTOR activation. Therefore, regular exercise intermittently activates antioxidant 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 withactivators 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 ofAMPK activation could also prevent negative consequences of the cellular hyperenergization. It is believed that the decline of both antioxidant and proliferativepotentials of the cells causes the age-dependent decline of multiple tissues, rather thanonly the muscular one. We argue that the approach above is applicable for the majorityof tissues in an organism.