PMID- 32586228
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20211204
IS  - 1608-3040 (Electronic)
IS  - 0006-2979 (Linking)
VI  - 85
IP  - 6
DP  - 2020 Jun
TI  - Manipulating Cellular Energetics to Slow Aging of Tissues and Organs.
PG  - 651-659
LID - 10.1134/S0006297920060024 [doi]
AB  - 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.
FAU - Sokolov, S S
AU  - Sokolov SS
AD  - Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical 
      Biology, Moscow, 119991, Russia.
FAU - Severin, F F
AU  - Severin FF
AD  - Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical 
      Biology, Moscow, 119991, Russia. severin@belozersky.msu.ru.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Biochemistry (Mosc)
JT  - Biochemistry. Biokhimiia
JID - 0376536
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Aging/*physiology
MH  - Animals
MH  - *Energy Metabolism
MH  - *Exercise
MH  - Humans
MH  - Mitochondria
MH  - Muscle, Skeletal/*metabolism
MH  - *Oxidative Stress
MH  - Phosphorylation
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2020/06/27 06:00
MHDA- 2021/01/05 06:00
CRDT- 2020/06/27 06:00
PHST- 2020/06/27 06:00 [entrez]
PHST- 2020/06/27 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
AID - BCM85060763 [pii]
AID - 10.1134/S0006297920060024 [doi]
PST - ppublish
SO  - Biochemistry (Mosc). 2020 Jun;85(6):651-659. doi: 10.1134/S0006297920060024.