Biological Age Testing: Which Epigenetic Clocks Are Worth Using in 2025
Your chronological age is the number of years you have been alive. Your biological age is the age your cells and tissues actually function at - and the two can diverge by decades. Epigenetic clocks now allow direct measurement of biological age from a blood sample, and have advanced far enough to become clinically actionable tools.
- Epigenetic clocks measure biological age from patterns of DNA methylation at specific CpG sites. The deviation between estimated biological age and chronological age - epigenetic age acceleration - is the clinically relevant output.
- First generation clocks (Horvath, Hannum) predicted chronological age accurately. Second generation clocks (PhenoAge, GrimAge) were trained to predict mortality and age-related disease - making them more clinically informative for longevity purposes.
- DunedinPACE measures the pace of aging rather than a static age estimate - making it uniquely sensitive to intervention effects. The CALERIE caloric restriction trial found DunedinPACE significantly slowed with CR while other clocks did not detect the effect.
- GrimAge is the most predictive single clock for all-cause mortality, Alzheimer's risk, cardiovascular events, and cancer risk. An individual with GrimAge significantly above their chronological age is in a genuinely higher-risk biological state.
- Commercial epigenetic age testing is available at 200 to 400 dollars through TruDiagnostic and Elysium Health. The most clinically valuable test includes both a GrimAge estimate and a DunedinPACE measurement.
The idea that biological age might diverge significantly from chronological age has been a central intuition of aging science for decades. What changed in 2013 was the discovery by Steve Horvath at UCLA that the pattern of DNA methylation marks across the genome predicts chronological age with astonishing accuracy - so accurately that a blood sample could be used to estimate a person's age to within a few years without any other information.1 More importantly, individuals whose methylation pattern was older than their chronological age had worse health outcomes and higher mortality.
How Epigenetic Clocks Work
DNA methylation is the addition of a methyl group to cytosine nucleotides at CpG sites. Methylation patterns change systematically with age across hundreds of CpG sites - some sites becoming more methylated, others less - in a pattern highly conserved across individuals and tissues. An epigenetic clock is a machine learning algorithm trained on methylation data from thousands of individuals of known ages, producing an estimated biological age from methylation levels at a specific set of CpG sites.2
The Clock Generations
First Generation (Horvath and Hannum): Trained to predict chronological age accurately (median error 3.6 years) but less sensitive to health-relevant biological aging.3 Second Generation (PhenoAge and GrimAge): Trained to predict biological phenotype and mortality respectively. GrimAge trained on surrogate biomarkers of age-related disease is the most clinically predictive of all available clocks for hard health outcomes - significantly predicting all-cause mortality, cardiovascular disease, cancer, Alzheimer's disease, and physical disability in multiple large prospective cohort studies.4 Third Generation (DunedinPACE): Estimates the pace of aging rather than a static age. A DunedinPACE of 1.0 means aging at the average pace; 0.8 means aging 20 percent slower. The CALERIE trial found DunedinPACE significantly slowed with caloric restriction while other clocks did not detect the effect.5
"GrimAge tells you where you are. DunedinPACE tells you how fast you are getting there. Together they give you the most complete picture of biological aging available from a single blood draw."
Dr. Morgan Levine, Yale University, developer of PhenoAgeWhat Accelerates and Slows Biological Age
| Factor | Effect on GrimAge/DunedinPACE | Effect Size |
|---|---|---|
| Smoking | Dramatically accelerates both | Large (+5 to +10 years GrimAge) |
| Regular aerobic exercise | Slows both | Moderate to large |
| Mediterranean diet adherence | Slows GrimAge | Moderate |
| Caloric restriction (CALERIE) | Significantly slows DunedinPACE | Significant |
| Poor sleep / sleep apnea | Accelerates both | Moderate |
References
- 1Horvath S. "DNA methylation age of human tissues and cell types." Genome Biology. 2013;14(10):R115. [PubMed]
- 2Jones PA. "Functions of DNA methylation: islands, start sites, gene bodies and beyond." Nature Reviews Genetics. 2012;13(7):484-492. [PubMed]
- 3Hannum G, et al. "Genome-wide methylation profiles reveal quantitative views of human aging rates." Molecular Cell. 2013;49(2):359-367. [PubMed]
- 4Lu AT, et al. "DNA methylation GrimAge strongly predicts lifespan and healthspan." Aging (Albany NY). 2019;11(2):303-327. [PubMed]
- 5Belsky DW, et al. "DunedinPACE, a DNA methylation biomarker of the pace of aging." eLife. 2022;11:e73420. [PubMed]