# Epigenetic drift

Epigenetic drift is the slow, mostly random divergence of DNA methylation patterns over time. It happens between cells, between tissues, and between people, as you age. The landmark demonstration came from Fraga and colleagues (2005, PNAS). They studied identical twins. Twins start life nearly epigenetically identical. But they accumulate big differences in their methylation and histone marks with age and environment. Drift differs from the clock-like methylation changes that power Horvath-style age estimators. Drift adds noise and makes cells less alike. The clock signal, by contrast, is directional. Issa (2014) framed drift as a vicious cycle. Environmental insults degrade the epigenome and predispose to age-related disease and cancer. Drift is now a recognized hallmark of aging.

## Sources

- Fraga MF, Ballestar E, Paz MF, et al.. (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0500398102
- Issa JP. (2014). Aging and epigenetic drift: a vicious cycle. Journal of Clinical Investigation. https://doi.org/10.1172/JCI69735
- Lopez-Otin C, Blasco MA, Partridge L, et al.. (2023). Hallmarks of aging: An expanding universe. Cell. https://doi.org/10.1016/j.cell.2022.11.001

---

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