Amino Acid Sensing in Skeletal Muscle

Tatiana Moro; Scott M Ebert; Christopher M Adams; Blake B Rasmussen

doi:10.1016/j.tem.2016.06.010

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Amino Acid Sensing in Skeletal Muscle

Tatiana Moro, Scott M Ebert, Christopher M Adams and Blake B Rasmussen

Trends in endocrinology and metabolism, Vol.27(11), pp.796-806

11/2016

DOI: 10.1016/j.tem.2016.06.010

PMCID: PMC5075248

PMID: 27444066

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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. Aging impairs endothelial cell function in skeletal muscle, thereby reducing delivery of dietary amino acids to skeletal muscle fibers. Aging promotes anabolic resistance by impairing the ability of amino acids, insulin, or muscle contraction to increase protein synthesis in skeletal muscle. Anabolic resistance may originate with endothelial dysfunction and impaired amino acid delivery to skeletal muscle fibers, thereby generating two distinct amino acid starvation responses [decreased mammalian/mechanistic target of rapamycin complex 1 (mTORC1) activity and increased activating transcription factor 4 (ATF4) activity], which reduce muscle protein synthesis, leading to muscle weakness and atrophy. Potential therapeutic strategies include restoration of amino acid delivery to aged skeletal muscle via increased physical activity, dietary protein, pharmacologic vasodilators, and/or small molecules that stimulate mTORC1 and/or inhibit ATF4 in aged skeletal muscle fibers.

leucine

general control nonderepressible 2

mammalian/mechanistic target of rapamycin complex 1

tomatidine

activating transcription factor 4

ursolic acid

Details

Title: Subtitle: Amino Acid Sensing in Skeletal Muscle
Creators: Tatiana Moro - Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, TX, USA
Scott M Ebert - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Christopher M Adams - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Blake B Rasmussen - Department of Nutrition and Metabolism, University of Texas Medical Branch, Galveston, TX, USA
Resource Type: Journal article
Publication Details: Trends in endocrinology and metabolism, Vol.27(11), pp.796-806
DOI: 10.1016/j.tem.2016.06.010
PMID: 27444066
PMCID: PMC5075248
NLM abbreviation: Trends Endocrinol Metab
ISSN: 1043-2760
eISSN: 1879-3061
Publisher: Elsevier Ltd
Language: English
Date published: 11/2016
Academic Unit: Molecular Physiology and Biophysics; Internal Medicine
Record Identifier: 9984025599702771

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