2024-03-28T12:14:50Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/92462022-10-25T09:37:15Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
00925njm 22002777a 4500
dc
Segales, Jessica
author
Perdiguero, Eusebio
author
Serrano, Antonio L
author
Sousa-Victor, Pedro
author
Ortet, Laura
author
JardĂ, Mercè
author
Budanov, Andrei V
author
Garcia-Prat, Laura
author
Sandri, Marco
author
Thomson, David M
author
Karin, Michael
author
Hee Lee, Jun
author
Munoz-Canoves, Pura
author
2020-01
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.
Nat Commun. 2020; 11(1):189
2041-1723
http://hdl.handle.net/20.500.12105/9246
31929511
10.1038/s41467-019-13832-9
2041-1723
Nature communications
Sestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals