Impaired expression of Notch signaling genes in aged human skeletal muscle

J Gerontol A Biol Sci Med Sci. 2007 Jan;62(1):9-17. doi: 10.1093/gerona/62.1.9.

Abstract

Notch signaling is essential for myogenesis and the regenerative potential of skeletal muscle; however, its regulation in human muscle is yet to be fully characterized. Increased expression of Notch3, Jagged1, Hes1, and Hes6 gene transcripts were observed during differentiation of cultured human skeletal muscle cells. Furthermore, significantly lower expressions of Notch1, Jagged1, Numb, and Delta-like 1 were evident in muscle biopsies from older men (60-75 years old) compared to muscle from younger men (18-25 years old). Importantly, with supervised resistance exercise training, expression of Notch1 and Hes6 genes were increased and Delta-like 1 and Numb expression were decreased. The differences in Notch expression between the age groups were no longer evident following training. These results provide further evidence to support the role of Notch in the impaired regulation of muscle mass with age and suggest that some of the benefits provided by resistance training may be mediated through the Notch signaling pathway.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aging / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Biopsy
  • Blotting, Western
  • Calcium-Binding Proteins / genetics
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Drosophila Proteins
  • Female
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Jagged-1 Protein
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / physiology*
  • Nerve Tissue Proteins / genetics
  • Physical Exertion / physiology
  • RNA, Messenger / genetics*
  • Receptor, Notch1 / genetics
  • Receptor, Notch3
  • Receptors, Notch / genetics*
  • Receptors, Notch / metabolism
  • Regeneration / genetics
  • Repressor Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serrate-Jagged Proteins
  • Signal Transduction / genetics
  • Transcription Factor HES-1

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • DLK1 protein, human
  • Drosophila Proteins
  • HES6 protein, human
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • NOTCH1 protein, human
  • NOTCH3 protein, human
  • Nerve Tissue Proteins
  • NUMB protein, human
  • RNA, Messenger
  • Receptor, Notch1
  • Receptor, Notch3
  • Receptors, Notch
  • Repressor Proteins
  • Ser protein, Drosophila
  • Serrate-Jagged Proteins
  • Transcription Factor HES-1
  • HES1 protein, human