Amino Acid Sensing in Skeletal Muscle

Tatiana Moro, Scott M. Ebert, Christopher M. Adams, Blake Rasmussen

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
JournalTrends in Endocrinology and Metabolism
DOIs
StateAccepted/In press - 2016

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Skeletal Muscle
Activating Transcription Factor 4
Amino Acids
Muscle Proteins
Skeletal Muscle Fibers
Muscular Atrophy
Muscle Weakness
Sarcopenia
Dietary Proteins
Muscle Strength
Muscle Contraction
Starvation
Vasodilator Agents
Endothelial Cells
Insulin
mechanistic target of rapamycin complex 1
Proteins

Keywords

  • Activating transcription factor 4
  • General control nonderepressible 2
  • Leucine
  • Mammalian/mechanistic target of rapamycin complex 1
  • Tomatidine
  • Ursolic acid

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Amino Acid Sensing in Skeletal Muscle. / Moro, Tatiana; Ebert, Scott M.; Adams, Christopher M.; Rasmussen, Blake.

In: Trends in Endocrinology and Metabolism, 2016.

Research output: Contribution to journalArticle

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