Article

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
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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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