DNA methylation age of blood predicts all-cause mortality in later life.
Level 3 - non-randomized controlled study
Meta-analysis of non-randomized longitudinal cohort studies and pedigree-based heritability analysis
PubMed 25633388 · doi:10.1186/s13059-015-0584-6
What was done
The authors evaluated whether the discrepancy between chronological age and blood DNA methylation age (Δage) predicts all-cause mortality in older adults. Δage was assessed across four longitudinal cohorts, and proportional hazards models were combined via meta-analysis. Analyses adjusted for age, sex, childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status. A pedigree-based analysis in an independent cohort was also performed to estimate the heritability of Δage.
What was found
A 5-year higher Δage was associated with a 21% higher all-cause mortality risk after adjusting for age and sex. Following further adjustment for socio-demographic factors, disease history, and APOE e4 status, a 5-year higher Δage remained associated with a 16% increase in mortality risk. The pedigree-based heritability estimate for Δage was 0.43.
Why it matters
This study demonstrates that DNA methylation age in blood reflects aspects of biological aging beyond simple chronological age and provides independent prognostic value for mortality risk.
Limits
Total sample size across cohorts and follow-up duration are not reported in the abstract. The study is observational and restricted to older populations, limiting generalizability to younger individuals and precluding causal inference. Specific confidence intervals and exact hazard ratios are omitted in the abstract.
Cited by
- supports Faster biological aging as measured by DNA methylation epigenetic clocks predicts shorter lifespan, worse health, and earlier mortality.