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Sestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals

Authors: Laura García-Prat; Laura García-Prat; Laura García-Prat; Andrei V. Budanov; Andrei V. Budanov; David M. Thomson; Michael Karin; +12 Authors

Sestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals

Abstract

AbstractA unique property of skeletal muscle is its ability to adapt its mass to changes in activity. Inactivity, as in disuse or aging, causes atrophy, the loss of muscle mass and strength, leading to physical incapacity and poor quality of life. Here, through a combination of transcriptomics and transgenesis, we identify sestrins, a family of stress-inducible metabolic regulators, as protective factors against muscle wasting. Sestrin expression decreases during inactivity and its genetic deficiency exacerbates muscle wasting; conversely, sestrin overexpression suffices to prevent atrophy. This protection occurs through mTORC1 inhibition, which upregulates autophagy, and AKT activation, which in turn inhibits FoxO-regulated ubiquitin–proteasome-mediated proteolysis. This study reveals sestrin as a central integrator of anabolic and degradative pathways preventing muscle wasting. Since sestrin also protected muscles against aging-induced atrophy, our findings have implications for sarcopenia.

Countries
United States, Portugal, Spain, Italy
Keywords

Male, Aging, Sarcopenia, Science, Medical Physiology, 610, Skeletal muscle, Gene Expression, Muscle Proteins, Mice, Transgenic, Mechanistic Target of Rapamycin Complex 1, Inbred C57BL, Transgenic, Article, Mice, 616, Autophagy, 2.1 Biological and endogenous factors, Animals, Humans, Aetiology, Muscle, Skeletal, Heat-Shock Proteins, Biomedical and Clinical Sciences, Animal, Forkhead Box Protein O1, Prevention, Q, Forkhead Box Protein O3, Nuclear Proteins, Skeletal, Mice, Inbred C57BL, Disease Models, Animal, Muscular Atrophy, Musculoskeletal, Disease Models, Proteolysis, Muscle, Signal Transduction

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
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106
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