TY - JOUR
T1 - Amino Acid Sensing in Skeletal Muscle
AU - Moro, Tatiana
AU - Ebert, Scott M.
AU - Adams, Christopher M.
AU - Rasmussen, Blake B.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (R56 AG051267, P30 AG024832, R43 AG044898, R43 AR069400, and R41 AG047684), the Department of Veterans Affairs Biomedical Laboratory Research & Development Service (IBX000976A), the Department of Veterans Affairs Rehabilitation Research and Development Service (1I01RX001477), and the Fraternal Order of Eagles Diabetes Research Center at the University of Iowa.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - activating transcription factor 4
KW - general control nonderepressible 2
KW - leucine
KW - mammalian/mechanistic target of rapamycin complex 1
KW - tomatidine
KW - ursolic acid
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U2 - 10.1016/j.tem.2016.06.010
DO - 10.1016/j.tem.2016.06.010
M3 - Review article
C2 - 27444066
AN - SCOPUS:84978842077
SN - 1043-2760
VL - 27
SP - 796
EP - 806
JO - Trends in Endocrinology and Metabolism
JF - Trends in Endocrinology and Metabolism
IS - 11
ER -