Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging

J Appl Physiol (1985). 2008 May;104(5):1452-61. doi: 10.1152/japplphysiol.00021.2008. Epub 2008 Mar 6.


Skeletal muscle loss during aging leads to an increased risk of falls, fractures, and eventually loss of independence. Resistance exercise is a useful intervention to prevent sarcopenia; however, the muscle protein synthesis (MPS) response to resistance exercise is less in elderly compared with young subjects. On the other hand, essential amino acids (EAA) increase MPS equally in both young and old subjects when sufficient EAA is ingested. We hypothesized that EAA ingestion following a bout of resistance exercise would stimulate anabolic signaling and MPS similarly between young and old men. Each subject ingested 20 g of EAA 1 h following leg resistance exercise. Muscle biopsies were obtained before and 1, 3, and 6 h after exercise to measure the rate of MPS and signaling pathways that regulate translation initiation. MPS increased early in young (1-3 h postexercise) and later in old (3-6 h postexercise). At 1 h postexercise, ERK1/2 MNK1 phosphorylation increased and eIF2alpha phosphorylation decreased only in the young. mTOR signaling (mTOR, S6K1, 4E-BP1, eEF2) was similar between groups at all time points, but MNK1 phosphorylation was lower at 3 h and AMP-activated protein kinase-alpha (AMPKalpha) phosphorylation was higher in old 1-3 h postexercise. We conclude that the acute MPS response after resistance exercise and EAA ingestion is similar between young and old men; however, the response is delayed with aging. Unresponsive ERK1/2 signaling and AMPK activation in old muscle may be playing a role in the delayed activation of MPS. Notwithstanding, the combination of resistance exercise and EAA ingestion should be a useful strategy to combat sarcopenia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Aged
  • Aging / physiology*
  • Algorithms
  • Amino Acids, Essential / pharmacology*
  • Anabolic Agents / pharmacology*
  • Blotting, Western
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Glucose / metabolism
  • Glycogen Synthase Kinase 3 / biosynthesis
  • Glycogen Synthase Kinase 3 beta
  • Hormones / blood
  • Humans
  • Hydrocortisone / blood
  • Lactic Acid / metabolism
  • Leucine / blood
  • Leucine / pharmacology
  • Male
  • Middle Aged
  • Muscle Proteins / biosynthesis*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / growth & development*
  • Muscle, Skeletal / metabolism*
  • Phenylalanine / blood
  • Phosphorylation
  • Physical Fitness / physiology*
  • Protein Kinases / biosynthesis
  • RNA / biosynthesis
  • RNA / isolation & purification
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases


  • Amino Acids, Essential
  • Anabolic Agents
  • Hormones
  • Muscle Proteins
  • Lactic Acid
  • Phenylalanine
  • RNA
  • Protein Kinases
  • MTOR protein, human
  • Glycogen Synthase Kinase 3 beta
  • TOR Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • Glycogen Synthase Kinase 3
  • Leucine
  • Glucose
  • Hydrocortisone