title: Amino Acid Sensing in Skeletal Muscle.
abstract: Aging impairs skeletal muscle protein synthesis, leading to muscle weakness and atrophy. However, the underlying molecular mechanisms remain poorly understood. Here, we review evidence that mammalian/mechanistic target of rapamycin complex 1 (mTORC1)-mediated and activating transcription factor 4 (ATF4)-mediated amino acid (AA) sensing pathways, triggered by impaired AA delivery to aged skeletal muscle, may play important roles in skeletal muscle aging. Interventions that alleviate age-related impairments in muscle protein synthesis, strength, and/or muscle mass appear to do so by reversing age-related changes in skeletal muscle AA delivery, mTORC1 activity, and/or ATF4 activity. An improved understanding of the mechanisms and roles of AA sensing pathways in skeletal muscle may lead to evidence-based strategies to attenuate sarcopenia.
authors.affiliation: Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Moro
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA; Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Ebert
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA; Iowa City Veterans Affairs Medical Center, Iowa City, IA, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Adams
authors.affiliation: Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, TX, USA; Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: blrasmus@utmb.edu.
authors.forename: Blake B
authors.initials: BB
authors.lastname: Rasmussen
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014315:Triterpenes / Q000378:metabolism; D000097245:Ursolic Acid
chemical_list: D051701:Activating Transcription Factor 4; D000596:Amino Acids; D058570:TOR Serine-Threonine Kinases; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: activating transcription factor 4; general control nonderepressible 2; leucine; mammalian/mechanistic target of rapamycin complex 1; tomatidine; ursolic acid