A breakthrough study published in the journal Nature Aging in 2025 gave the answer: In healthy elderly people over 70 years old, daily supplementation of Omega-3 unsaturated fatty acids (1 gram/day) can significantly slow down the rate of biological aging, and combined supplementation of vitamin D (2000 IU/day) and moderate exercise have better effects. This study, called DO-HEALTH, tracked 777 European elderly people for 3 years and revealed for the first time the molecular mechanism of nutritional intervention on aging through the DNA methylation (DNAm) clock.
To understand the significance of this study, we must first recognize an emerging aging assessment tool-DNA methylation clock.
DNA methylation is an epigenetic modification in the human body. As we age, the methylation marks on DNA change. By analyzing hundreds of thousands of methylation sites, scientists have developed a variety of "clock" algorithms that can compare biological age with actual age.
First-generation clocks (such as Horvath clocks): mainly predict actual age, but have a weak correlation with disease.
Second-generation clocks (such as PhenoAge, GrimAge): constructed through blood biochemical indicators and mortality data, can predict the risk of diseases such as heart disease and cancer.
Third-generation clocks (such as DunedinPACE): directly measure the rate of aging through the rate of change of 19 organ function indicators.
In the DO-HEALTH study, Omega-3 supplementation significantly slowed the aging rate of the three clocks. Supplementation of unsaturated fatty acids, if evaluated by the PhenoAge clock, can slow down the biological age by 0.16 standard deviations (equivalent to 2.9 months), and if evaluated by GrimAge2, it slowed down by 0.32 standard deviations (equivalent to 3.8 months). When evaluated by the third-generation DunedinPACE, the aging rate of the supplementer was reduced by 0.17 standard deviations (about 1% of the annual aging rate).
Omega-3: An all-rounder against aging
Omega-3 (especially DHA and EPA) is an unsaturated fatty acid rich in deep-sea fish and algae. Studies have found that its anti-aging effect is reflected in three levels.
On the one hand, Omega-3 fatty acids play a role in regulating epigenetics. Omega-3 inhibits the expression of pro-inflammatory and pro-aging genes by changing the DNA methylation pattern.
For example:
The role of unsaturated fatty acids on the PAI-1 gene cannot be ignored. High expression of this gene will hinder the decomposition of blood clots. Omega-3 significantly reduces its methylation level, which is equivalent to reducing the risk of vascular aging.
In addition, Omega-3 supplementation significantly reduces leptin-related methylation, which helps to improve metabolic disorders.
In previous studies, the same team found that among 2,157 elderly people, Omega-3 can reduce the risk of infection by 13% and the risk of falling by 10%. If combined with vitamin D and exercise, the incidence of cancer is reduced by 61%.
Who will benefit the most from supplementing Omega-3 unsaturated fatty acids? The study showed that participants with a baseline blood omega-3 concentration of ≤100 ng/mL had a more significant effect on slowing epigenetic aging after supplementation (the effect size increased by 30%). This may be related to the higher level of inflammation in people with omega-3 deficiency.
Vitamin D: An underestimated "anti-aging ally"
Although vitamin D supplementation alone did not significantly affect the DNAm clock, its synergistic effect with omega-3 supplementation and exercise cannot be ignored.
When vitamin D (≥20 ng/mL) is used in combination with omega-3, PhenoAge's aging-slowing effect is increased by 50%. This may be related to vitamin D's enhanced immune regulation function.
The DO-HEALTH study found that combined supplementation of vitamin D and omega-3 can reduce the risk of "pre-frailty" by 39%. Reduced muscle mass loss is directly associated with a slower aging rate.
It should be noted that the dose of vitamin D in the study was 2000 IU/day, which exceeds the conventional recommended amount (800-1000 IU/day). This high-dose supplementation method needs to be used under the guidance of a doctor.
Home exercise: a low-cost anti-aging solution
The "Simple Home Exercise Program" (SHEP) in the study requires strength training 3 times a week, 30 minutes each time. Although exercise alone did not significantly change the DNAm clock, it was found that it had a more significant effect on anti-aging when combined with nutritional supplements.
Scientific research has found that resistance exercises such as squats and elastic band training can be given priority in home training. Each training session contains 8-10 movements and each set is repeated 10-15 times.
Who should be supplemented the most? How to grasp the dosage?
According to the above research results, the following groups should be supplemented with Omega-3 unsaturated fats and vitamin D the most-
Healthy elderly people over 70 years old: Studies have confirmed that this group has the most significant benefits.
Omega-3 deficiency (blood DHA+EPA<100 ng/mL): can be improved by salmon, sardines or high-purity fish oil supplements.
Vitamin D deficiency (serum 25(OH)D<20 ng/mL): common in areas with insufficient sunlight.
In terms of supplementation dosage, here are some suggestions.
Omega-3: 1 gram per day (containing DHA 660 mg + EPA 330 mg), equivalent to eating deep-sea fish 3 times a week.
Vitamin D: 2000 IU per day, blood calcium levels need to be checked regularly to prevent overdose.
Risk warning: High doses of fish oil may increase the risk of bleeding, and those taking anticoagulants need to consult a professional doctor.
Although the results are exciting, they need to be viewed rationally. The study lasted only 3 years, and whether the delayed biological age of 2.9-3.8 months can be converted into a longer life span still needs longer tracking. The participants were all healthy elderly people in Europe, and the benefits for people in other regions are not yet clear. Research data show that there is a 20%-30% individual fluctuation in epigenetic response. This huge individual difference may be related to genotype, which is also worth noting.
In 2021, the American Heart Association (AHA) proposed a "mind-heart-body" holistic health model, which coincides with the conclusion of this study. Aging is not an irreversible "one-way street". The DO-HEALTH study used rigorous data to prove that the reasonable supplementation of Omega-3 and vitamin D, combined with moderate exercise, can press the "deceleration key" of aging at the molecular level. Of course, any intervention should be carried out under the guidance of a doctor. After all, the ultimate secret to longevity is the combination of scientific cognition and self-disciplined life.