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

Aging Cell

Lorna W. Harries³  Luke C. Pilling⁶  L. Dena G. Hernandez¹  Rachel Bradley-Smith³  William Henley⁶  Andrew B. Singleton¹  Jack M. Guralnik⁴  Stefania Bandinelli²  Luigi Ferrucci⁵ 

[1] Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA;Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy;Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK;Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD, USA;National Institute on Aging, Baltimore, MD, USA;Epidemiology and Public Health, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK

关键词: inflammation;    macrophage;    mechanism;    population;    regeneration;    transcription;   

DOI  :  10.1111/j.1474-9726.2011.00782.x

来源: Wiley

【 摘 要 】

Summary

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 35.2 kg compared with 41.2 kg 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.

【 授权许可】

Unknown   
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland