# Epigenetic alterations

Epigenetic alterations are age-related changes in how your genes are switched on and off, without any change to the DNA code itself. They include shifts in DNA methylation, in the chemical marks on histone proteins, in how chromatin is folded, and in non-coding RNAs. As you age, a typical pattern emerges: your DNA loses methylation overall but gains it in specific spots, heterochromatin loosens, and gene activity changes. These shifts are exactly what 'epigenetic clocks' read. First-generation clocks (like the Horvath clock) estimate your calendar age. Second-generation clocks (like PhenoAge and GrimAge) go further and predict death and disease risk, beyond what your age alone says.

## Sources

- Horvath & Raj. (2018). DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nature Reviews Genetics. https://doi.org/10.1038/s41576-018-0004-3
- López-Otín et al.. (2023). Hallmarks of aging: An expanding universe. Cell. https://doi.org/10.1016/j.cell.2022.11.001

---

_Canonical: https://longevity-switzerland.com/en/glossary/epigenetic-alterations · Part of Longevity Cities · Updated 2026-06-22_