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Partial inhibition of mTORC1 in aged rats counteracts the decline in muscle mass and reverses molecular signaling associated with sarcopenia

Joseph, Giselle and Shavlakadze, Tea and Glass, David and Wang, Sharon and Zhou, Weihua and Tse, Herman and Jacobs, Cody and Eash, John and Kimble, Garrett (2019) Partial inhibition of mTORC1 in aged rats counteracts the decline in muscle mass and reverses molecular signaling associated with sarcopenia. Molecular and Cellular Biology, 39 (19). ISSN 10985549

Abstract

There is a lack of pharmacological interventions available for sarcopenia, a progressive age-associated loss of muscle mass, leading to a decline in mobility and quality of life. We found mTORC1 (mammalian target of rapamycin complex 1), a well-established positive modulator of muscle mass, to be surprisingly hyperactivated in sarcopenic muscle. Furthermore, partial inhibition of the mTORC1 pathway counteracted sarcopenia, as determined by observing an increase in muscle mass and fiber type cross-sectional area in select muscle groups, again surprising because mTORC1 signaling has been shown to be required for skeletal muscle mass gains in some models of hypertrophy. Additionally, several genes related to senescence were downregulated and gene expression indicators of neuromuscular junction denervation were diminished using a low dose of a "rapalog" (a pharmacological agent related to rapamycin). Therefore, partial mTORC1 inhibition may delay the progression of sarcopenia by directly and indirectly modulating multiple age-associated pathways, implicating mTORC1 as a therapeutic target to treat sarcopenia.

Item Type: Article
Keywords: Aging MTOR MTORC1 Muscle Rapalog Rapamycin Sarcopenia Skeletal muscle
Date Deposited: 18 Jan 2020 00:45
Last Modified: 18 Jan 2020 00:45
URI: https://oak.novartis.com/id/eprint/39059

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