Table 3.
Studies selected for review pertaining to "epigenetic clocks" or DNA methylation biomarkers of aging.
| DNA Methylation “Clocks” | ||||
|---|---|---|---|---|
| Study Title | BA Predictor Used | Cohort Name (If Applicable) | n | Results |
| DNA methylation GrimAge strongly predicts lifespan and healthspan | GrimAge | Framingham Heart Study Offspring Cohort | 2356 | Predictive ability for time-to-death (Cox regression p=2.0E-75), time-to-coronary heart disease (Cox p=6.2E-24), and time-to-cancer (p= 1.3E-12) (Lu et al., 2019) |
| DNA methylation age of human tissues and cell types | DNAm age “Horvath Clock” | 82 publicly available datasets | 7844 | The multi-tissue age predictor performs remarkably well in most tissues and cell types. (Age correlation 0.97, error = 2.9 years) (Horvath, 2013) |
| Genome-wide methylation profiles reveal quantitative views of human aging rates | “Hannum Clock” | 656 | Correlation between age and predicted age of 96% and an error of 3.9 years (Hannum et al., 2013) | |
| An epigenetic biomarker of aging for lifespan and healthspan | PhenoAge | Women’s Health Initiative (WHI), the Framingham Heart Study (FHS), the Normative Aging Study (NAS), and the Jackson Heart Study (JHS) | 2016, 2191, 2553, 657, 1747 | A one-year increase in DNAm PhenoAge is associated with a 4.5% increase in the risk of all-cause mortality (Meta (FE) = 1.045, meta p=7.9E-47 (Levine et al., 2018) |
| Longitudinal trajectories, correlations, and mortality associations of nine biological ages across 20-year follow-up | Telomere length, DNAm age (4 types), physiological age, cognitive function, functional aging index, and frailty index | Swedish population-based cohort | 845 | Individually, all BAs except for telomere length were associated with mortality risk independently of CA. The largest effects were seen for methylation age estimators (GrimAge) and the frailty index (FI) (Li et al., 2020) |
| DNA methylation-based measures of biological age: meta-analysis predicting time to death | Horvath and Hannum | 13 cohorts | 13,089 | All considered measures of epigenetic age acceleration were predictive of mortality (p ≤ 8.2 × 10−9) (Chen et al., 2016) |
| DNA methylation signatures in peripheral blood strongly predict all-cause mortality | Zhang 10 CpG clock | 1900 | Demonstrated that a risk score based on DNAm of ten identified CpGs was a very strong predictor for all-cause, CVD, and cancer mortality (Zhang et al., 2017) | |