The DO-HEALTH trial tested vitamin D, omega-3, and exercise on epigenetic clocks in 800 generally healthy adults aged 70 and older over three years.
The PhenoAge epigenetic clock uses methylation at 500 CpG sites and incorporates clinical biomarkers like albumin and CRP to predict mortality risk.
GrimAge uses methylation at 1,000 CpG sites to estimate levels of plasma proteins linked to aging and smoking exposure, combining them with age and sex to predict time to death.
The DunedinPACE clock uses 173 CpG sites in a longitudinal model trained on the Dunedin cohort to estimate an individual's pace of aging, rather than a static biological age.
In the DO-HEALTH trial, omega-3 supplementation showed a significant but small effect on three of the four epigenetic clocks, translating roughly to three months of reduced aging over the three-year study.
The vitamin D intervention in DO-HEALTH used 2,000 IU daily, which Attia considered modest; 30% of participants had baseline levels below 20 ng/dL.
Life insurance companies use proprietary actuarial models to predict mortality with extreme accuracy but do not currently incorporate commercially available biological aging clocks.
Peter Attia argues that while aging clocks are a promising research tool for compressing multidimensional aging into a single metric, they currently lack proven clinical utility for individual health decisions.
Aging clocks are susceptible to both biological noise, like transient inflammation from a workout, and technical measurement noise from sample handling and lab processing.
Attia notes that proven biomarkers like blood pressure, glucose, and lipid levels have decades of evidence linking them directly to clinical outcomes, unlike current aging clock scores.