Perna · Clinical epigenetics 2016 · case-cohort study · n=1863

Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort.

Cited 633 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective case-cohort observational study with multivariable survival analysis

PubMed 27274774 · doi:10.1186/s13148-016-0228-z · record verified 2026-08-30

What was done

DNA methylation age was estimated in a population-based case-cohort study of 1,863 older German individuals. Epigenetic age acceleration (the difference between DNA methylation age and chronological age, Δage) was calculated using both Horvath and Hannum epigenetic clocks. Weighted Cox proportional hazards models were used to evaluate associations between 5-year increments of Δage and all-cause, cancer, and cardiovascular mortality, adjusting for batch effects, age, sex, educational level, history of chronic diseases, hypertension, smoking status, body mass index, and leukocyte distribution.

What was found

Per 5-year increase in Horvath epigenetic age acceleration: - All-cause mortality: HR 1.23 (95% CI 1.10–1.38) - Cancer mortality: HR 1.22 (95% CI 1.03–1.45) - Cardiovascular mortality: HR 1.19 (95% CI 0.98–1.43) Associations were reported as similar but weaker for the Hannum clock, but specific effect sizes were not provided in the abstract.

Why it matters

The paper demonstrates that epigenetic age acceleration independently predicts all-cause and cancer mortality in older adults, supporting its utility as a biomarker of biological aging.

Limits

The cohort is restricted to older German adults, limiting generalizability. Cardiovascular mortality was not statistically significant after multivariable adjustment. Specific numbers for Hannum clock estimates, total death counts, and follow-up duration were omitted from the abstract.

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