Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults

Micah J. Drummond, Jared M. Dickinson, Christopher S. Fry, Dillon K. Walker, David M. Gundermann, Paul T. Reidy, Kyle L. Timmerman, Melissa M. Markofski, Douglas Paddon-Jones, Blake B. Rasmussen, Elena Volpi

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Skeletal muscle atrophy during bed rest is attributed, at least in part, to slower basal muscle protein synthesis (MPS). Essential amino acids (EAA) stimulate mammalian target of rapamycin (mTORC1) signaling, amino acid transporter expression, and MPS and are necessary for muscle mass maintenance, but there are no data on the effect of inactivity on this anabolic mechanism. We hypothesized that bed rest decreases muscle mass in older adults by blunting the EAA stimulation of MPS through reduced mTORC1 signaling and amino acid transporter expression in older adults. Six healthy older adults (67 ± 2 yr) participated in a 7-day bed rest study. We used stable isotope tracers, Western blotting, and real-time qPCR to determine the effect of bed rest on MPS, muscle mTORC1 signaling, and amino acid transporter expression and content in the postabsorptive state and after acute EAA ingestion. Bed rest decreased leg lean mass by ~4% (P < 0.05) and increased postabsorptive mTOR protein (P < 0.05) levels while postabsorptive MPS was unchanged (P > 0.05). Before bed rest acute EAA ingestion increased MPS, mTOR (Ser 2448), S6 kinase 1 (Thr 389, Thr 421/Ser 424), and ribosomal protein S6 (Ser 240/244) phosphorylation, activating transcription factor 4, L-type amino acid transporter 1 and sodium-coupled amino acid transporter 2 protein content (P < 0.05). However, bed rest blunted the EAA-induced increase in MPS, mTORC1 signaling, and amino acid transporter protein content. We conclude that bed rest in older adults significantly attenuated the EAA-induced increase in MPS with a mechanism involving reduced mTORC1 signaling and amino acid transporter protein content. Together, our data suggest that a blunted EAA stimulation of MPS may contribute to muscle loss with inactivity in older persons.

Original languageEnglish (US)
Pages (from-to)E1113-E1122
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume302
Issue number9
DOIs
StatePublished - May 1 2012

Keywords

  • L-type amino acid transporter
  • Mammalian target of rapamycin
  • Physical inactivity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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    Drummond, M. J., Dickinson, J. M., Fry, C. S., Walker, D. K., Gundermann, D. M., Reidy, P. T., Timmerman, K. L., Markofski, M. M., Paddon-Jones, D., Rasmussen, B. B., & Volpi, E. (2012). Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. American Journal of Physiology - Endocrinology and Metabolism, 302(9), E1113-E1122. https://doi.org/10.1152/ajpendo.00603.2011