Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/9246
Título
Sestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals
Autor(es)
Fecha de publicación
2020-01
Cita
Nat Commun. 2020; 11(1):189
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
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