The epigenetic clock as a predictor of disease and mortality risk: a systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of observational cohort studies
PubMed 30975202 · doi:10.1186/s13148-019-0656-7
What was done
A systematic review and meta-analysis was conducted according to PRISMA guidelines across MEDLINE, Embase, Cochrane CENTRAL, and PsychINFO. Investigators included studies evaluating peripherally measured DNA methylation age acceleration as a predictor of longevity, age-related diseases (cancer, cardiovascular disease, and dementia), or all-cause mortality. Joanna Briggs Institute critical appraisal checklists were used to evaluate bias. Two meta-analyses (one per epigenetic clock) evaluated all-cause mortality risk.
What was found
Twenty-three articles encompassing 41,607 participants met inclusion criteria (4 on longevity, 11 on age-related disease, and 11 on mortality). Meta-analyses found that each 5-year increase in DNA methylation age was associated with an 8% to 15% increased risk of all-cause mortality. Associations between increased epigenetic age and specific age-related diseases or longevity were inconsistent or inconclusive, with no specific effect sizes reported in the abstract.
Why it matters
This synthesis demonstrates that DNA methylation age acceleration predicts all-cause mortality across large human cohorts, although its diagnostic or prognostic utility for specific chronic diseases remains unconfirmed.
Limits
The abstract notes high heterogeneity in study designs and outcome measures, a small number of studies for disease-specific endpoints, and potential positive publication bias for mortality findings. Exact numerical risk estimates, clock types, and confidence intervals were not reported in the abstract.
Cited by
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