Abstract
SummaryMicroRNAs (miRNAs) regulate gene expression with emerging data suggesting miRNAs play a role in skeletal muscle biology. We sought to examine the association of miRNAs with grip strength in a community‐based sample. Framingham Heart Study Offspring and Generation 3 participants (n = 5668 54% women, mean age 55 years, range 24, 90 years) underwent grip strength measurement and miRNA profiling using whole blood from fasting morning samples. Linear mixed‐effects regression modeling of grip strength (kg) versus continuous miRNA ‘Cq’ values and versus binary miRNA expression was performed. We conducted an integrative miRNA–mRNA coexpression analysis and examined the enrichment of biologic pathways for the top miRNAs associated with grip strength. Grip strength was lower in women than in men and declined with age with a mean 44.7 (10.0) kg in men and 26.5 (6.3) kg in women. Among 299 miRNAs interrogated for association with grip strength, 93 (31%) had FDR q value < 0.05, 54 (18%) had an FDR q value < 0.01, and 15 (5%) had FDR q value < 0.001. For almost all miRNA–grip strength associations, increasing miRNA concentration is associated with increasing grip strength. miR‐20a‐5p (FDR q 1.8 × 10−6) had the most significant association and several among the top 15 miRNAs had links to skeletal muscle including miR‐126‐3p, miR‐30a‐5p, and miR‐30d‐5p. The top associated biologic pathways included metabolism, chemokine signaling, and ubiquitin‐mediated proteolysis. Our comprehensive assessment in a community‐based sample of miRNAs in blood associated with grip strength provides a framework to further our understanding of the biology of muscle strength.
Highlights
Hand grip strength is a simple and inexpensive measure of muscle strength associated with exceptional survival (Willcox et al, 2006), allcause mortality, cardiovascular mortality, and cardiovascular disease (Leong et al, 2015)
Our investigation focused on Framingham Heart Study (FHS) Offspring participants who attended examination cycle 8 (2005–2008, n = 3021)
Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd
Summary
Hand grip strength is a simple and inexpensive measure of muscle strength associated with exceptional survival (Willcox et al, 2006), allcause mortality, cardiovascular mortality, and cardiovascular disease (Leong et al, 2015). Grip strength declines with age in both men and women (Dodds et al, 2014) and is used as a criterion of frailty as well as to define sarcopenia (low muscle mass and weakness; Studenski et al, 2014), which are important causes of disability and death in the community (Rodriguez-Manas & Fried, 2014). Genetic factors contribute substantially to the variability in grip strength (Frederiksen et al, 2002), suggesting that genetic studies may identify biologically relevant pathways important to muscle strength and aging. Few genomewide association studies have been conducted of grip strength (Chan et al, 2015; Matteini et al, 2016) with one identifying a promising common variant in a chromosomal region linked to muscle repair (Matteini et al, 2016)
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