Epigenetic Clocks and the Pace of Aging: What Recent Trials Show

By Dr. Ryan Kneessi, ND · Move Forward Natural Health, Odenton, MD · Last reviewed: October 19, 2026

Most of us know our age in years, yet two people born in the same year can age very differently. Some stay strong and sharp well into their eighties, while others start to lose ground much earlier. Researchers have spent the past decade trying to measure that difference directly, and one of the most promising tools they have built is the epigenetic clock. These tests are now sold to the public, which makes it worth understanding what they measure, what the trials actually show, and where the science still has limits.

What epigenetic alterations have to do with aging

Your DNA sequence stays largely the same throughout life, but the way your cells read it changes. Small chemical tags called methyl groups attach to specific spots on the DNA and help switch genes on or off. As we age, that methylation pattern drifts in predictable ways. Aging researchers count these epigenetic alterations as one of the 12 hallmarks of aging, alongside processes such as mitochondrial decline, cellular senescence, and chronic low-grade inflammation, which you can read more about in my article on inflammaging.

Because the drift is so consistent, scientists can feed methylation data from a blood sample into an algorithm and estimate a biological age. The first clocks were trained simply to predict a person’s age in years. Newer versions, such as PhenoAge and GrimAge, were trained to track blood chemistry and mortality risk, so they say more about health than about the calendar. Methylation itself depends on nutrients like folate and B12, which is one reason I also look at markers covered in methylation and homocysteine balance when someone is curious about how they are aging.

DunedinPACE measures speed instead of age

One of the most useful newer tools is DunedinPACE. Instead of estimating how old you are biologically, it estimates how fast you are aging right now. Researchers built it by following about a thousand people born in the same city in the early 1970s and tracking 19 measures of organ function over two decades. They then trained a methylation algorithm to capture that rate from a single blood draw. A score of 1.0 means roughly one year of biological aging per calendar year, so a lower number means a slower pace.

In the 2022 paper that introduced it, DunedinPACE showed high test–retest reliability, which matters a great deal for any test you might want to repeat. It was also associated with illness, disability, and mortality across five other datasets, and it added predictive information beyond GrimAge. The free full text is here: DunedinPACE, a DNA methylation biomarker of the pace of aging.

What the CALERIE calorie restriction trial found

CALERIE was a randomized controlled trial in 220 healthy adults without obesity, aged roughly 21 to 50. About two thirds were assigned to cut calories by 25 percent for two years, and the rest kept eating as usual. Most people in the calorie restriction group did not reach the full target, and the average reduction they actually achieved was closer to 12 percent.

Even so, a 2023 analysis of their blood samples found that the calorie restriction group had a slower pace of aging by DunedinPACE at both one and two years, which the authors estimated as a 2 to 3 percent slower rate. The older-style clocks, including PhenoAge and GrimAge, did not change significantly. The researchers described the effect as small and noted that responses varied widely from person to person. They also emphasized that longer follow-up is needed to know whether this change in a blood measure translates into longer, healthier lives. The free full text is here: Effect of long-term caloric restriction on DNA methylation measures of biological aging in the CALERIE trial.

I do not read this as a reason for anyone to start a strict diet. It tells us that a sustained, moderate change in how much people ate was enough to nudge a well-validated aging measure in the right direction. That is encouraging for anyone who wants to work on metabolic health through food and daily habits, and it fits with what we see in research on supporting autophagy without long fasts.

What the DO-HEALTH trial found about omega-3, vitamin D, and exercise

DO-HEALTH was a three-year randomized, double-blind, placebo-controlled trial in generally healthy adults aged 70 and older living in five European countries. Participants were assigned to vitamin D at 2,000 IU a day, omega-3s at 1 gram a day (330 mg EPA plus 660 mg DHA from algae), a home strength-training program three times a week, any combination of these, or placebo and a flexibility program. A 2025 analysis measured four newer epigenetic clocks in 777 participants at the start and after three years.

Omega-3 alone slowed three of the four measures: PhenoAge, GrimAge2, and DunedinPACE. The size of the effect worked out to roughly three months of slower biological aging over three years. For PhenoAge, combining omega-3 with vitamin D, strength training, or both produced an additive benefit. Vitamin D and exercise on their own did not change the clocks, and none of the interventions moved the first-generation clocks. The authors described the overall effect as small but protective. The free full text is here: Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks in the DO-HEALTH trial.

Three months over three years may not sound dramatic, but it came from a simple daily intervention in people who were already fairly healthy, and it was tested against placebo. If you are wondering whether omega-3s make sense for you, my guide on who should consider omega-3s walks through blood testing and safety, and the companion piece on vitamin D3 covers how to check your level first.

How to think about epigenetic age tests

These trials are exciting, but they come with important caveats. Both were post hoc analyses, meaning the clocks were measured after the trials were designed around other goals. The effects were averages, and individual results moved in both directions. Commercial epigenetic age tests also use different algorithms, so a number from one company cannot be compared directly with a number from another, and a single result can bounce around from normal lab variation.

In practice, I see an epigenetic clock as one data point rather than a verdict. It can be interesting to track over time if you use the same test each time, but it does not replace the basics. Standard functional lab markers for blood sugar, lipids, inflammation, and nutrients are often more actionable, and simple functional measures like grip strength tell you a lot about reserve and resilience.

The encouraging message from this research is that biological aging appears to respond to the same things we already know matter. Eating in a way that supports metabolic health, getting enough omega-3 fats, staying strong, and protecting sleep are all reasonable places to start, and they are worth doing whether or not you ever order a methylation test.

Frequently asked questions

Sources

• Belsky et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022. Free full text on PubMed Central.
• Waziry et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nature Aging. 2023. Free full text on PubMed Central.
• Bischoff-Ferrari et al. Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial. Nature Aging. 2025. Free full text on PubMed Central.

This article is for educational purposes only and is not medical advice. It does not replace an individual evaluation. Talk with your healthcare provider before starting a new supplement, changing your diet significantly, or changing medications, especially if you are pregnant, nursing, or managing a health condition.