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

Jessica Segalés, Eusebio Perdiguero, Antonio L. Serrano, Pedro Sousa-Victor, Laura Ortet, Mercè Jardí, Andrei V. Budanov, Laura Garcia-Prat, Marco Sandri, David M. Thomson, Michael Karin, Jun Hee Lee and Pura Muñoz-Cánoves ()
Additional contact information
Jessica Segalés: CIBERNED
Eusebio Perdiguero: CIBERNED
Antonio L. Serrano: CIBERNED
Pedro Sousa-Victor: CIBERNED
Laura Ortet: CIBERNED
Mercè Jardí: CIBERNED
Andrei V. Budanov: Trinity College Dublin
Laura Garcia-Prat: CIBERNED
Marco Sandri: University of Padova
David M. Thomson: Brigham Young University
Michael Karin: University of California San Diego
Jun Hee Lee: University of Michigan
Pura Muñoz-Cánoves: CIBERNED

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract A 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13832-9

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DOI: 10.1038/s41467-019-13832-9

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