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Human Skeletal Muscle Protein Metabolism Responses to Amino Acid Nutrition

Mitchell, W Kyle; Wilkinson, Daniel J; Phillips, Bethan E; Lund, Jonathan N; Smith, Kenneth; Atherton, Philip J


W Kyle Mitchell

Daniel J Wilkinson

Professor of Translational Physiology

Clinical Associate Professor

Professor of Metabolic Mass Spectrometry

Philip J Atherton


Healthy individuals maintain remarkably constant skeletal muscle mass across much of adult life, suggesting the existence of robust homeostatic mechanisms. Muscle exists in dynamic equilibrium whereby the influx of amino acids (AAs) and the resulting increases in muscle protein synthesis (MPS) associated with the intake of dietary proteins cancel out the efflux of AAs from muscle protein breakdown that occurs between meals. Dysregulated proteostasis is evident with aging, especially beyond the sixth decade of life. Women and men aged 75 y lose muscle mass at a rate of ∼0.7% and 1%/y, respectively (sarcopenia), and lose strength 2- to 5-fold faster (dynapenia) as muscle “quality” decreases. Factors contributing to the disruption of an otherwise robust proteostatic system represent targets for potential therapies that promote healthy aging. Understanding age-related impairments in anabolic responses to AAs and identifying strategies to mitigate these factors constitute major areas of interest. Numerous studies have aimed to identify 1) the influence of distinct protein sources on absorption kinetics and muscle anabolism, 2) the latency and time course of MPS responses to protein/AAs, 3) the impacts of protein/AA intake on muscle microvascular recruitment, and 4) the role of certain AAs (e.g., leucine) as signaling molecules, which are able to trigger anabolic pathways in tissues. This review aims to discuss these 4 issues listed, to provide historical and modern perspectives of AAs as modulators of human skeletal muscle protein metabolism, to describe how advances in stable isotope/mass spectrometric approaches and instrumentation have underpinned these advances, and to highlight relevant differences between young adults and older individuals. Whenever possible, observations are based on human studies, with additional consideration of relevant nonhuman studies.


Mitchell, W. K., Wilkinson, D. J., Phillips, B. E., Lund, J. N., Smith, K., & Atherton, P. J. (2016). Human Skeletal Muscle Protein Metabolism Responses to Amino Acid Nutrition. Advances in Nutrition, 7(4), 828S-838S.

Journal Article Type Article
Acceptance Date Jul 1, 2016
Online Publication Date Jul 15, 2016
Publication Date Jul 25, 2016
Deposit Date Jun 10, 2019
Journal Advances in Nutrition: An International Review Journal
Print ISSN 2156-5376
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 7
Issue 4
Pages 828S-838S
Public URL
Publisher URL