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

Aging Cell

Artem Zykovich³  Alan Hubbard⁴  James M. Flynn³  Mark Tarnopolsky²  Mario F. Fraga⁵  Chad Kerksick¹  Dan Ogborn²  Lauren MacNeil²  Sean D. Mooney³ 

[1] Department of Health, Exercise and Sport Sciences, University of New Mexico, Albuquerque, NM, USA;Neuromuscular and Neurometabolic Unit, Rm. 2H26, McMaster Children's Hospital, McMaster University Medical Center, Hamilton, Ontario, Canada;Buck Institute for Research on Aging, Novato, CA, USA;Division of Biostatistics, School of Public Health, University of California, Berkeley, CA, USA;Cancer Epigenetics Laboratory, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CNB-CSIC, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain

关键词: DNA methylation;    skeletal muscle;    human aging;    epigenome;    genomics;    postmitotic;   

DOI  :  10.1111/acel.12180

来源: Wiley

【 摘 要 】

Summary

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 overrepresented 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 an 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 postmitotic skeletal muscle and DNA methylation.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.