CCAAT-enhancer-binding protein-beta expression in vivo is associated with muscle strength
Lorna W. Harries
Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
Search for more papers by this authorLuke C. Pilling
Epidemiology and Public Health, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
Search for more papers by this authorL. Dena G. Hernandez
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
Search for more papers by this authorRachel Bradley-Smith
Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
Search for more papers by this authorWilliam Henley
Epidemiology and Public Health, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
School of Mathematics and Statistics, University of Plymouth, Plymouth, UK
Search for more papers by this authorAndrew B. Singleton
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
Search for more papers by this authorJack M. Guralnik
Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD, USA
Search for more papers by this authorStefania Bandinelli
Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy
Search for more papers by this authorDavid Melzer
Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
Search for more papers by this authorLorna W. Harries
Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
Search for more papers by this authorLuke C. Pilling
Epidemiology and Public Health, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
Search for more papers by this authorL. Dena G. Hernandez
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
Search for more papers by this authorRachel Bradley-Smith
Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
Search for more papers by this authorWilliam Henley
Epidemiology and Public Health, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
School of Mathematics and Statistics, University of Plymouth, Plymouth, UK
Search for more papers by this authorAndrew B. Singleton
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
Search for more papers by this authorJack M. Guralnik
Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD, USA
Search for more papers by this authorStefania Bandinelli
Geriatric Unit, Azienda Sanitaria di Firenze, Florence, Italy
Search for more papers by this authorDavid Melzer
Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter EX1 2LU, UK
Search for more papers by this authorSummary
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.
Supporting Information
Table S1 Top 250 microarray probes (genes) associated with handgrip strength (kg).
Table S2 Regression based estimated of C/EBP-ß expression associations with measures of strength.
Table S3 Odds ratio for having impaired performance on performance scores, comparing those with top tertile CEBP-ß expression to lowest tertile expression.
Fig. S1 Microarray Validation – Hand Grip strength by tertiles of C\EBP-β expression measured by TLDA, for 100 men with middle tertile lymphocyte and neutrophil percentages.
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