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Key Highlights

• Omega-3 (fish oil) slows your body’s clock. A new 3‑year study in 777 adults (average age ~75) that received 1 g/day of omega-3 found it slowed three DNA “aging clocks” (PhenoAge, GrimAge2, DunedinPACE) by a small but significant amount.
  This amounted to about 2.9–3.8 months less biological aging over three years (roughly 1 month per year).
• Vitamin D and exercise alone didn’t budge the clocks. The study also tested 2,000 IU/day of vitamin D and a home exercise program (30 min strength/flexibility, 3×/week). By themselves, neither vitamin D nor exercise changed the epigenetic ages.
  However, when all three interventions were combined, there was an extra boost: the PhenoAge clock ticked even more slowly.
• More proof fish oil matters: health wins. In the same DO‑HEALTH trial, daily omega-3 cut infections by ~13% and falls by ~10%. Even better, the full combo (omega-3 + vitamin D + exercise) together cut new prefrailty cases by ~39% and invasive cancer risk by ~61% over 3 years.
  In other words, these simple interventions not only nudge molecular aging clocks, they also translate to real-world health gains.

What is an Epigenetic Clock?

Think of an epigenetic clock like a little odometer built into your DNA. As we age, chemical tags (DNA methylation) accumulate at certain spots on our genes.

Scientists have trained algorithms (clocks) to read those tags and predict biological age, which may differ from calendar age. Unlike birth certificates, epigenetic clocks try to measure how “worn out” our bodies are.

Leading clocks have names like PhenoAge and GrimAge, which are built from dozens or hundreds of DNA markers. These “next-generation clocks” are strongly linked to health outcomes – faster ticking ones usually mean higher risk of disease and mortality.

In short, slower tick = possibly longer, healthier life.

The DO‑HEALTH Trial – A Big Test in Seniors

DO‑HEALTH is a large European clinical trial of healthy aging in adults 70+ years old. It used a 2×2×2 factorial design (8 groups) to test three cheap, non-drug interventions:

• Vitamin D3 (2,000 IU per day) – a dose many doctors prescribe to boost bone and immune health.
• Omega‑3 fatty acids (1,000 mg per day) – a typical fish oil supplement (EPA+DHA).
• Simple home exercise (30 min, 3×/week) – a strength-focused routine older adults can do without a gym.

Over 3 years, 2,157 participants were randomized to take each supplement or sham pill (placebo), and do or not do the exercise program. They tracked dozens of health outcomes (blood pressure, fractures, cognition, etc.).

In an ancillary study called DO‑HEALTH Bio-Age, a subset of 777 participants had their blood analyzed for DNA methylation at the start and end. The goal: see if these interventions slow “molecular aging.”

What the Study Found – Omega-3 Wins (Mostly)

The results (published in Nature Aging) were pretty clear:

• Omega‑3 supplement slowed aging clocks. Participants taking 1 g/day of omega-3 had slower increases in biological age on 3 of the 4 clocks tested. In statistical terms, their age-acceleration scores for PhenoAge, GrimAge2, and DunedinPACE were each reduced (PhenoAge by 0.16 units, GrimAge2 by 0.32, DunedinPACE by 0.17).
  In plain English, the omega-3 group’s epigenetic age increased more slowly, amounting to about 3–4 months younger biological age over 3 years.
• Vitamin D alone – no effect on clocks. The daily 2,000 IU vitamin D supplement did not change any of the clocks on its own. (This was true even though many older adults tend to be low in vitamin D.)
  In other words, taking vitamin D by itself did not measurably slow or speed up the epigenetic aging markers in this study.

• Exercise alone – also no change. The 30‑minute home exercise routine (done three times per week) alone did not significantly alter the clocks. This doesn’t mean exercise isn’t good – it just didn’t move the DNA methylation clock in this analysis (likely because effects were smaller or varied).
  The older adults did get the usual fitness benefits, but on the molecular-age front, no clock effect was detected.
• All three combined give extra benefit on PhenoAge. Even though vitamin D and exercise alone did little, there was an additive effect when they were layered on top of omega-3.
  In the PhenoAge clock, every combination that included omega-3 (with or without vitamin D/exercise) slowed aging a bit more. The strongest slowdown (effect size ~ –0.32) was seen when all three interventions were used together.
  In practical terms, the epigenetic age was lowest when older adults both took the supplements and did the exercise program.
• Magnitude of the effect. It’s important to keep perspective: the clock changes were statistically significant but small. The study reports that from start to year‑3, the standardized differences ranged 0.16–0.32 units, which they equate to roughly 2.9–3.8 months of younger biological age.
  So it’s not like a decade was taken off your cells, but even a few months could be meaningful over a lifespan.

Why This Matters for Health

You might wonder: “So what? A few months?” In aging research, even modest slowdowns can add up.

Epigenetic clocks are linked to diseases. As Horvath et al. explain, these DNA markers offer accurate age estimates and help answer “why do we age?”.

More importantly, other studies suggest that a slightly slower clock can translate to real health gains.

For example, the CALERIE calorie-restriction trial (another 2-year RCT) found a 2–3% slower pace of aging (by DunedinPACE) from eating 25% fewer calories. The authors point out that even small slowing of aging “can have profound effects on population health” down the line.

In the case of DO‑HEALTH, we see those benefits in hard outcomes:

• Those on daily omega-3 had 13% fewer infections and 10% fewer falls than non-users.
• And when all three interventions were combined, new prefrailty cases dropped by ~39%, and invasive cancer incidence dropped by ~61% over 3 years.

These are big numbers. They suggest that slowing down your molecular aging even a little might mean better health and resilience as you get older.

In plain terms: fish oil and vitamin D (plus exercise) aren’t magic bullets, but they seem to gently nudge your body into a healthier, more robust state.

Think of it as adding reinforcement to your “healthy aging” toolbox.

Putting it in Context of Healthy Living

This study fits with a growing body of research on diet, supplements and aging clocks. Previous observational and small studies hinted at similar ideas.

For instance, low vitamin D has been linked with faster epigenetic aging, and one analysis found that giving vitamin D supplements to deficient seniors lowered their DNA age acceleration by over a year.

Exercise and diet patterns have shown mixed results on clocks – sometimes active people have “younger” DNA, but it’s complex.

DO‑HEALTH is one of the first large trials to test these questions head-to-head. Its take-home is: fish oil supplementation shows a measurable anti-aging signal, vitamin D or moderate exercise add no extra clock benefit alone, but the trio together give a slight edge on one key clock.

That doesn’t mean skip sunshine or the gym – just that for DNA methylation aging measures, omega-3 was the standout in this group.

Take-Home Tips for Readers

If you’re 35+ and thinking about ways to stay younger longer, here are some practical, science-backed moves aligned with this study:

• Consider omega-3s. Eating fatty fish (salmon, mackerel, sardines) a couple times a week or taking a daily fish-oil supplement (~1 g EPA+DHA) may modestly slow your biological clock.
  Aim for a quality supplement (look for “1 g omega-3” on the label). Omega-3s have other proven perks too (heart and brain health), so this tip is low risk and high reward.

• Get enough vitamin D. Even though vitamin D didn’t change the clocks alone in DO‑HEALTH, it is important for bone and immune health. Many adults 35+ are low in vitamin D.
  Have your levels checked; if low, a maintenance dose (1000–2000 IU/day) can bring you to a healthy range. Think of it as an insurance policy – and it may only boost your anti-aging program when combined with the others.
• Move regularly. DO‑HEALTH used a home exercise routine (30 min strength/flexibility, 3×/week). In general, aim for at least 150 minutes of moderate exercise per week, including strength training.
  Weight-bearing and resistance workouts preserve muscle and bone, and even if they didn’t show up on the DNA clock, they will improve your metabolism, balance, mood, and longevity. (As one researcher quipped: “Exercise can’t turn back the clock on this DNA test – but it definitely keeps other clocks running smoothly!”)

• Eat a healthy diet. This study focused on supplements, but whole foods matter. A Mediterranean-style diet rich in omega-3s, veggies, and antioxidants likely supports healthy aging.
  Plant-based omega-3 (flax, walnuts) count too, but EPA/DHA from fish or algae is most potent. Combine good nutrition with the supplements, and let them all team up against aging.

• Prioritize sleep and stress management. Healthy sleep and low stress are proven to protect your DNA. Chronically poor sleep or high stress can accelerate aging markers.
  Even if not part of this trial, don’t neglect these basics – they are free “anti-aging” strategies.
• Talk to your doctor. Before starting any new supplement (even vitamins), get medical advice. For example, high-dose omega-3 or vitamin D can interact with medications or conditions. Your doctor can check blood levels and tailor recommendations for you.

In summary: a daily fish-oil capsule and a little strength exercise won’t magically rewind all wrinkles or make you immortal.

But this study suggests they may shave a bit off your cells’ age-odometer. That may not sound like much, but slow, steady progress in healthy aging can add up over decades.

As researchers note, even a modest slowdown in aging-related decline “can have profound effects on population health.”

So why not help your body stay a few months younger, and stack the odds in favor of better health as you age?

References

[1] Bischoff-Ferrari HA 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;5(2):123–134. doi:10.1038/s43587-024-00793-y.

[2] Bischoff-Ferrari HA et al. DO‑HEALTH: Vitamin D3–Omega-3–Home exercise–Healthy aging trial – design and rationale of a multicenter clinical trial. Contemp Clin Trials 2021;100:106124. doi:10.1016/j.cct.2020.106124.

[3] Waziry R et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults (CALERIE trial). Nature Aging 2023;3:248–257. doi:10.1038/s43587-022-00357-y.

[4] Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nature Rev Genet 2018;19:371–384. doi:10.1038/s41576-018-0004-3.

[5] Vetter VM et al. Vitamin D supplementation is associated with slower epigenetic aging. Geroscience 2022;44:1847–1859. doi:10.1007/s11357-022-00581-9.

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