2026-04-28T22:57:01Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/92462024-10-31T11:42:20Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Segales, Jessica author Perdiguero, Eusebio author Serrano, Antonio L author Sousa-Victor, Pedro author Ortet, Laura author Jardí, 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