Increased ceramide content and NFκB signaling may contribute to the attenuation of anabolic signaling after resistance exercise in aged males

J Appl Physiol (1985). 2012 Dec 1;113(11):1727-36. doi: 10.1152/japplphysiol.00412.2012. Epub 2012 Oct 4.


One of the most fundamental adaptive physiological events is the response of skeletal muscle to high-intensity resistance exercise, resulting in increased protein synthesis and ultimately larger muscle mass. However, muscle growth in response to contraction is attenuated in older humans. Impaired contractile-induced muscle growth may contribute to sarcopenia: the age-associated loss of muscle mass and function that is manifested by loss of strength, contractile capacity, and endurance. We hypothesized that the storage of ceramide would be increased in older individuals and this would be associated with increases in NFκB signaling and a decreased anabolic response to exercise. To test this hypothesis we measured ceramides at rest and anabolic and NFκB signaling after an acute bout of high-intensity resistance exercise in young and older males. Using lipidomics analysis we show there was a 156% increase in the accumulation of C16:0-ceramide (P < 0.05) and a 30% increase in C20:0-ceramide (P < 0.05) in skeletal muscle with aging, although there was no observable difference in total ceramide. C16:0-ceramide content was negatively correlated (P = 0.008) with lower leg lean mass. Aging was associated with a ~60% increase in the phosphorylation of the proinflammatory transcription factor NFκB in the total and nuclear cell fractions (P < 0.05). Furthermore, there was an attenuated activation of anabolic signaling molecules such as Akt (P < 0.05), FOXO1 (P < 0.05), and S6K1 (P < 0.05) after an acute bout of high-intensity resistance exercise in older males. We conclude that ceramide may have a significant role in the attenuation of contractile-induced skeletal muscle adaptations and atrophy that is observed with aging.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Age Factors
  • Aged
  • Aging / metabolism*
  • Aging / pathology
  • Analysis of Variance
  • Biopsy
  • Body Composition
  • Ceramides / metabolism*
  • Cytokines / blood
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Inflammation Mediators / blood
  • Male
  • Metabolomics
  • Muscle Contraction*
  • Muscle Strength
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Muscular Atrophy / physiopathology
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Protein Phosphatase 2 / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quadriceps Muscle / growth & development
  • Quadriceps Muscle / metabolism*
  • Quadriceps Muscle / pathology
  • Resistance Training*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction*
  • Time Factors
  • Up-Regulation
  • Young Adult


  • Ceramides
  • Cytokines
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Inflammation Mediators
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • Ribosomal Protein S6 Kinases, 70-kDa
  • ribosomal protein S6 kinase, 70kD, polypeptide 1
  • Protein Phosphatase 2