An analysis of a clinical trial involving 777 older adults suggests that daily omega-3 intake can moderately slow biological aging, with combined interventions showing the strongest effects on aging and disease prevention

A recent study published in Nature Aging reveals that omega-3 may moderately delay biological aging across several epigenetic clocks by up to four months.

The study also provides evidence supporting gero-protective benefits associated with additive combinations of omega-3, vitamin D, and exercise.

Background

Biological aging is the progressive deterioration of physiological functions in living organisms. A vast pool of studies have been conducted on animals and humans to understand the aging process and to identify interventions aimed at slowing down biological aging.

Both observational studies and small pilot trials have highlighted the effectiveness of vitamin D and omega-3 supplementation and exercise in slowing down biological aging. However, there remains a scarcity of larger clinical trials testing these treatments individually or in combination in humans.

The study

The study included 777 Swiss participants from the DO-HEALTH trial, who had DNA methylation data available at the trial baseline and the 3-year follow-up.  

The DO-HEALTH trial was a multicenter randomized controlled trial designed to support healthy longevity. Its primary aim was to investigate the effect of vitamin D and omega-3 supplementation and exercise, either individually or in combination, over three years.

The researchers used three second-generation epigenetic clocks and one third-generation epigenetic clock to calculate the rates of biological aging in these participants, who consumed 2,000 International units (IU) of vitamin D per day, took one gram of omega-3 per day, and participated in a 30-minute home exercise program three times a week, either separately or in combination, over the 3-year trial period.

Important observations

Researchers analyzed participant-derived blood samples for four epigenetic clocks and found daily omega-3 supplementation moderately reduces the biological aging of three out of four clocks by up to four months.

They controlled potential covariates in the analysis and found that these changes in DNA methylation measures of biological aging are not dependent on the age, sex, and body mass index (BMI) of participants.

Notably, they found additive benefits of combining omega-3, vitamin D, and exercise in terms of slowing down biological aging of one epigenetic clock. Specifically, they observed that the combination of these three interventions has the highest effect in lowering cancer risk and preventing frailty over three years.

Study significance

This DO-HEALTH Bio-Age study provides evidence about the effect of three interventions (omega-3, vitamin D, and exercise) on four next-generation DNA methylation measures of biological aging (epigenetic clocks) over three years.

The study finds a small protective effect of omega-3 supplementation on slowing down biological aging over three years across several epigenetic clocks. Furthermore, the study finds that these three interventions together have the highest impact in reducing cancer risk and preventing frailty over 3 years.

The clear impact of omega-3 supplementation observed in the study indicates a prominent epigenetic response and highlights the epigenetic impact of nutritional interventions on the biological aging process.

The study finds that participants with lower levels of omega-3 at baseline exhibit larger epigenetic shifts, suggesting that baseline nutritional status may modulate the extent of epigenetic responsiveness. This observation highlights the significance of omega-3 as a targeted intervention to influence biological aging.

Among the epigenetic clocks analyzed, the study finds the strongest effect on two second-generation clocks and one third-generation clock, which is in accordance with previous studies investigating the effects of lifestyle factors on biological aging.

Researchers highlight that a major limitation of the study is that there is no standardized measure of biological aging and that they opted for the most-validated epigenetic clocks available.

They also mention that DNA methylation measurements provide only a partial view of the aging-associated biological changes and come with certain technical limitations.

The study population, which includes only Swiss individuals, does not represent the general global population of adults aged 70 years or above, which may restrict the generalizability of the study findings.

The study investigates the changes in biological aging rates for only three years. It remains unknown to what extent these interventions influence epigenetic clocks in the long run. Future studies are needed to understand the effects of long-term interventions on biological aging.