DNA methylation of insulin signaling pathways is associated with HOMA2-IR in primary myoblasts from older adults.
Burton MA., Garratt ES., Hewitt MO., Sharkh HY., Antoun E., Westbury LD., Dennison EM., Harvey NC., Cooper C., MacIsaac JL., Kobor MS., Patel HP., Godfrey KM., Lillycrop KA.
BackgroundWhile ageing is associated with increased insulin resistance (IR), the molecular mechanisms underlying increased IR in the muscle, the primary organ for glucose clearance, have yet to be elucidated in older individuals. As epigenetic processes are suggested to contribute to the development of ageing-associated diseases, we investigated whether differential DNA methylation was associated with IR in human primary muscle stem cells (myoblasts) from community-dwelling older individuals.MethodsWe measured DNA methylation (Infinium HumanMethylationEPIC BeadChip) in myoblast cultures from vastus lateralis biopsies (119 males/females, mean age 78.24 years) from the Hertfordshire Sarcopenia Study extension (HSSe) and examined differentially methylated cytosine phosphate guanine (CpG) sites (dmCpG), regions (DMRs) and gene pathways associated with HOMA2-IR, an index for the assessment of insulin resistance, and levels of glycated hemoglobin HbA1c.ResultsThirty-eight dmCpGs (false discovery rate (FDR) ConclusionsThese findings suggest that insulin resistance is associated with differential DNA methylation in human primary myoblasts with both muscle mass and body composition making a significant contribution to the methylation changes associated with IR.