Genome-wide DNA methylation changes with age in disease-free human skeletal muscle

Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA, 94945, USA.
Aging cell (Impact Factor: 5.94). 11/2013; 13(2). DOI: 10.1111/acel.12180
Source: PubMed

ABSTRACT A decline in skeletal muscle mass and function with aging is well recognized, but remains poorly characterized at the molecular level. Here we report for the first time a genome-wide study of DNA methylation dynamics in skeletal muscle of healthy male individuals during normal human aging. We predominantly observed hypermethylation throughout the genome within the aged group as compared to the young subjects. Differentially methylated CpG (dmCpG) nucleotides tend to arise intragenically, and are underrepresented in promoters and are overrepresented in the middle and 3' end of genes. The intragenic methylation changes are over represented in genes that guide the formation of the junction of the motor neuron and myofibers. We report a low level of correlation of gene expression from previous studies of aged muscle with our current analysis of DNA methylation status. For those genes that had both changes in methylation and gene expression with age, we observed a reverse correlation, with the exception of intragenic hypermethylated genes, that were correlated with increased gene expression. We suggest that a minimal number of dmCpG sites or select sites are required to be altered in order to correlate with gene expression changes. Finally, we identified 500 dmCpG sites that perform well in discriminating young from old samples. Our findings highlight epigenetic links between aging post-mitotic skeletal muscle and DNA methylation. This article is protected by copyright. All rights reserved.

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Available from: Alan E Hubbard, Sep 15, 2014
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    • "The score of the methylation value associated with each CpG site was defined as the beta value multiplied by 1000, with the beta value in turn defined as the proportion of the intensity value from the methylated bead type from the sum of the intensity values from both methylated and unmethylated bead type plus 100. Published methylation data of primary cells from tissues of brain (Day et al., 2013; Kozlenkov et al., 2014; Wockner et al., 2014), muscle (Ribel-Madsen et al., 2012; Day et al., 2013; Zykovich et al., 2013), fat (Ribel-Madsen et al., 2012; Grundberg et al., 2013), and saliva (Liu et al., 2010; Bocklandt et al., 2011; Souren et al., 2013; Park et al., 2014) were obtained through Gene Expression Omnibus (GEO) (http:// (Edgar et al., 2002) and ArrayExpress ( (Rustici et al., 2012). "
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