Epigenetic alterations

Epigenetic alterations are age-related changes in DNA methylation patterns, histone modifications, chromatin architecture and non-coding RNA expression that occur without changes to the underlying DNA sequence. With age, the epigenome typically shows global hypomethylation alongside focal hypermethylation, loss of heterochromatin and altered transcription. These shifts underpin epigenetic clocks: first-generation chronological-age estimators such as the Horvath clock, and second-generation clocks like PhenoAge and GrimAge that predict mortality and disease risk above and beyond chronological age.