A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration.
Level 3 - non-randomized controlled study
Systematic review of predominantly observational studies
PubMed 33930583 · doi:10.1016/j.arr.2021.101348
What was done
Authors conducted a systematic review across four databases to synthesize evidence on biological, social, and environmental determinants of blood-based epigenetic clock acceleration or deceleration. From 156 included publications, they compiled an extraction dataset of over 1,300 study findings and performed statistical analyses on 57 distinct exposure-clock relationships evaluated across four major epigenetic clocks (Hannum, Horvath, Levine, and GrimAge).
What was found
The Horvath, Hannum, Levine, and GrimAge clocks broadly agreed in the direction of associations, though effect magnitudes varied. Epigenetic clock acceleration was significantly associated with male sex, elevated body mass index (BMI), and HIV infection. Accelerated epigenetic aging was also significantly related to clinical outcomes, including all-cause mortality, cardiovascular disease, cancer, and diabetes. The abstract reports directional findings and significance without specific effect sizes, confidence intervals, or test statistics.
Why it matters
This review aggregates a decade of epigenetic aging research, confirming that major blood-based clocks capture coherent signals of physiological stress, disease risk, and demographic traits despite algorithm-specific differences in effect size.
Limits
The synthesized evidence relies primarily on observational human data, precluding causal conclusions. The abstract does not provide numerical effect estimates, meta-analytic heterogeneity statistics, or formal quality assessments of included studies. Findings are restricted to blood tissue measurements and four specific clocks.
Cited by
- supports HIV infection is associated with accelerated epigenetic aging in humans.