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Manipulating Cellular Energetics to Slow Aging of Tissues and Organs

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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.

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Abbreviations

AICAR:

5-aminoimidazole-4-carboxamide ribonucleotide

AMPK:

AMP-dependent protein kinase

GH:

growth hormone

IGF1:

insulin-like growth factor 1

MGF:

muscle growth factor

mTOR:

mammalian target of rapamycin

ROS:

reactive oxygen species

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Funding

This work was supported by the Russian Foundation for Basic Research (project No. 19-14-50642).

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  1. Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991, Moscow, Russia

    S. S. Sokolov & F. F. Severin

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  1. S. S. Sokolov
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  2. F. F. Severin
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Correspondence to F. F. Severin.

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This article does not contain description of studies involving humans or animals as research subjects performed by any of the authors. The authors declare no conflict of interest.

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Sokolov, S., Severin, F. Manipulating Cellular Energetics to Slow Aging of Tissues and Organs. Biochemistry Moscow 85, 651–659 (2020). https://doi.org/10.1134/S0006297920060024

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