A new multiomics study analyzing pancreatic islets from 144 donors reveals that DNA methylation patterns associated with aging are fundamentally different from those linked to type 2 diabetes.
Researchers identified 996 age-associated and 902 diabetes-associated CpG methylation sites, with almost no overlap. Age-related changes were found in gene promoter regions and formed coordinated modules linked to beta cell function and insulin secretion. In contrast, diabetes-associated changes were more scattered across enhancer and non-regulatory regions, suggesting a stress-related epigenetic signature.
The team also developed a blood-based methylation risk score that, when combined with genetic risk, achieved strong discriminatory performance (AUC: 0.91) for classifying type 2 diabetes. Mendelian randomization suggested a causal role for age-related methylation changes in the gene KLHL42, a locus previously tied to diabetes risk.
The findings indicate that aging drives a coordinated biological process affecting beta cells, while diabetes reflects a more variable, stress-related epigenetic response. DNA methylation markers may offer new opportunities for early risk identification.