Amino Acid Sensing in Skeletal Muscle

Trends Endocrinol Metab. 2016 Nov;27(11):796-806. doi: 10.1016/j.tem.2016.06.010. Epub 2016 Jul 19.


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.

Keywords: activating transcription factor 4; general control nonderepressible 2; leucine; mammalian/mechanistic target of rapamycin complex 1; tomatidine; ursolic acid.

Publication types

  • Review

MeSH terms

  • Activating Transcription Factor 4 / metabolism
  • Amino Acids / metabolism*
  • Animals
  • Humans
  • Muscle, Skeletal / metabolism*
  • TOR Serine-Threonine Kinases / metabolism
  • Triterpenes / metabolism
  • Ursolic Acid


  • Amino Acids
  • Triterpenes
  • Activating Transcription Factor 4
  • TOR Serine-Threonine Kinases