Muscle-Specific SIRT1 Gain-of-Function Increases Slow-Twitch Fibers and Ameliorates Pathophysiology in a Mouse Model of Duchenne Muscular Dystrophy

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Skeletal muscle has a central role in body posture, mobility and whole-body metabolism. SIRT1 is an enzyme expressed in skeletal muscle, as well as in most mammalian tissues, and has been shown to sense metabolic cues from the environment and mediate changes in these tissues, counteracting age and metabolic diseases. Here we generated and studied mice that express high levels of SIRT1 in skeletal muscle. We found that increased levels of SIRT1 in skeletal muscle led to gene expression changes similar to those that normally occur with endurance exercise. We also observed that SIRT1 overexpression counteracts muscle atrophy, a hallmark of aging muscle, and the muscle degenerative disease Duchenne muscular dystrophy (DMD). DMD is a debilitating disease caused by a mutation in the structural protein dystrophin. SIRT1 overexpression ameliorated the pathophysiology of DMD disease in a mouse model. Our results offer the hope that drugs that constitutively activate the enzymatic activity of SIRT1 might be used to cure muscle degenerative diseases.

Vyšlo v časopise: Muscle-Specific SIRT1 Gain-of-Function Increases Slow-Twitch Fibers and Ameliorates Pathophysiology in a Mouse Model of Duchenne Muscular Dystrophy. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004490
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004490

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