RT Journal Article SR Electronic T1 Inhibition of mTORC1 signaling in aged rats counteracts the decline in muscle mass and reverses multiple parameters of muscle signaling associated with sarcopenia JF bioRxiv FD Cold Spring Harbor Laboratory SP 591891 DO 10.1101/591891 A1 Giselle A. Joseph A1 Sharon Wang A1 Weihua Zhou A1 Garrett Kimble A1 Herman Tse A1 John Eash A1 Tea Shavlakadze A1 David J. Glass YR 2019 UL http://biorxiv.org/content/early/2019/03/28/591891.abstract AB 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 critical positive modulator of mass, to be hyperactivated in sarcopenic muscle. Furthermore, inhibition of the mTORC1 pathway counteracted sarcopenia as determined by observing an increase in muscle mass and fiber type cross sectional area, surprising because mTORC1 signaling has been shown to be required for muscle mass gains in some settings. Additionally, several genes related to senescence were downregulated, while gene expression indicators of neuromuscular junction denervation were diminished using a low dose of a rapalog. Therefore 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.