CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength

Lorna W. Harries, Luke C. Pilling, L. Dena G Hernandez, Rachel Bradley-Smith, William Henley, Andrew B. Singleton, Jack M. Guralnik, Stefania Bandinelli, Luigi Ferrucci, David Melzer

Research output: Contribution to journalArticle

Abstract

Declining muscle strength is a core feature of aging. Several mechanisms have been postulated, including CCAAT/enhancer-binding protein-beta (C/EBP-β)-triggered macrophage-mediated muscle fiber regeneration after micro-injury, evidenced in a mouse model. We aimed to identify in vivo circulating leukocyte gene expression changes associated with muscle strength in the human adult population. We undertook a genome-wide expression microarray screen, using peripheral blood RNA samples from InCHIANTI study participants (aged 30 and 104). Logged expression intensities were regressed with muscle strength using models adjusted for multiple confounders. Key results were validated by real-time PCR. The Short Physical Performance Battery (SPPB) score tested walk speed, chair stand, and balance. CEBPB expression levels were associated with muscle strength (β coefficient=0.20560, P=1.03*10 -6, false discovery rate q=0.014). The estimated handgrip strength in 70-year-old men in the lowest CEBPB expression tertile was 35.2kg compared with 41.2kg in the top tertile. CEBPB expression was also associated with hip, knee, ankle, and shoulder strength and the SPPB score (P=0.018). Near-study-wide associations were also noted for TGF-β3 (P=3.4*10 -5, q=0.12) and CEBPD expression (P=9.7*10 -5, q=0.18) but not for CEBPA expression. We report here a novel finding that raised CEBPB expression in circulating leukocyte-derived RNA samples in vivo is associated with greater muscle strength and better physical performance in humans. This association may be consistent with mouse model evidence of CEBPB-triggered muscle repair: if this mechanism is confirmed, it may provide a target for intervention to protect and enhance aging muscle.

Original languageEnglish (US)
Pages (from-to)262-268
Number of pages7
JournalAging Cell
Volume11
Issue number2
DOIs
StatePublished - Apr 2012
Externally publishedYes

Keywords

  • Inflammation
  • Macrophage
  • Mechanism
  • Population
  • Regeneration
  • Transcription

ASJC Scopus subject areas

  • Cell Biology
  • Aging

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  • Cite this

    Harries, L. W., Pilling, L. C., Hernandez, L. D. G., Bradley-Smith, R., Henley, W., Singleton, A. B., Guralnik, J. M., Bandinelli, S., Ferrucci, L., & Melzer, D. (2012). CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength. Aging Cell, 11(2), 262-268. https://doi.org/10.1111/j.1474-9726.2011.00782.x