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 Fry, Dillon K. Walker, David M. Gundermann, Paul T. Reidy, Kyle L. Timmerman, Melissa M. Markofski, Douglas Paddon-Jones, Blake Rasmussen, Elena Volpi

Research output: Contribution to journalArticle

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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)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume302
Issue number9
DOIs
StatePublished - May 1 2012

Fingerprint

Amino Acid Transport Systems
Bed Rest
Essential Amino Acids
Muscle Proteins
Skeletal Muscle
Proteins
Muscles
Activating Transcription Factor 4
Eating
Ribosomal Protein S6
Ribosomal Protein S6 Kinases
Muscular Atrophy
mechanistic target of rapamycin complex 1
Sirolimus
Isotopes
Leg
Western Blotting
Sodium
Maintenance
Phosphorylation

Keywords

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

ASJC Scopus subject areas

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

Cite this

Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. / Drummond, Micah J.; Dickinson, Jared M.; Fry, Christopher; Walker, Dillon K.; Gundermann, David M.; Reidy, Paul T.; Timmerman, Kyle L.; Markofski, Melissa M.; Paddon-Jones, Douglas; Rasmussen, Blake; Volpi, Elena.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 302, No. 9, 01.05.2012.

Research output: Contribution to journalArticle

Drummond, Micah J. ; Dickinson, Jared M. ; Fry, Christopher ; Walker, Dillon K. ; Gundermann, David M. ; Reidy, Paul T. ; Timmerman, Kyle L. ; Markofski, Melissa M. ; Paddon-Jones, Douglas ; Rasmussen, Blake ; Volpi, Elena. / Bed rest impairs skeletal muscle amino acid transporter expression, mTORC1 signaling, and protein synthesis in response to essential amino acids in older adults. In: American Journal of Physiology - Endocrinology and Metabolism. 2012 ; Vol. 302, No. 9.
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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.",
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AU - Fry, Christopher

AU - Walker, Dillon K.

AU - Gundermann, David M.

AU - Reidy, Paul T.

AU - Timmerman, Kyle L.

AU - Markofski, Melissa M.

AU - Paddon-Jones, Douglas

AU - Rasmussen, Blake

AU - Volpi, Elena

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