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.

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.

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

Substances

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