Consuming 1 g of omega-3 per day may slow down the rate of biological aging in humans, a post-hoc analysis of DO-HEALTH trial data suggested.
DO-HEALTH tested the effects of three daily interventions — 2,000 IU of vitamin D, 1 g of omega-3, or a strength-training program — on older adults in Europe.
In a post-hoc study of 777 Swiss participants, 1 g of omega-3 daily slowed aging on three of four DNA methylation clocks — PhenoAge, GrimAge2, and DunedinPACE — over 3 years, reported Heike Bischoff-Ferrari, MD, DrPH, of the University of Zurich, and co-authors, in Nature Aging.
Standardized treatment effects ranged from 0.16 to 0.32 units from baseline to year 3, indicating that daily omega-3 slowed biological aging by 2.9 months to 3.8 months. This finding was not dependent on sex, age, or body mass index.
The three interventions tested in DO-HEALTH showed additive benefits on one epigenetic clock (PhenoAge), but not on the others.
“One of the most critical questions in the field of rejuvenation is whether a treatment exists that can effectively rejuvenate humans, not just mice,” Bischoff-Ferrari said.
“Given the well-documented health benefits of omega-3, we explored whether it also influences the most reliable molecular markers of biological age: epigenetic clocks,” she told MedPage Today. “Our findings show a robust signal that omega-3 supplementation — algae-based and 1 g per day — rejuvenated biological age by, on average, 3 months in 3 years.”
Main findings from the DO-HEALTH clinical trial showed that vitamin D, omega-3, or strength-training interventions did not lead to statistically significant differences in improvement of systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function in 2,157 older Europeans without major comorbidities.
Other DO-HEALTH analyses in small samples found that omega-3 lowered the risk of falling, while a combination of omega-3, vitamin D, and exercise lowered risks of pre-frailty and invasive cancer.
Clinical trials that investigate the effects of interventions to improve health during aging face two big challenges, noted Dame Linda Partridge, DPhil, of the University College London, who wasn’t involved with the study.
First, there are multiple possible outcome measures because many aspects of health could be affected. Second, it may take a long time for any benefits to become apparent, which is why biomarkers are needed, Partridge posted on the U.K. Science Media Centre web site.
The biomarkers investigated in this study were derived from several well-authenticated DNA methylation clocks, she pointed out. “These clocks are trained to predict biological, as opposed to chronological age,” she wrote. “Individuals differ in the speed of change in their DNA methylation clocks and can thus be characterized as slow or fast agers. These clock age deviations can be better predictors of time to death than chronological age.”
The analysis identified a beneficial effect of daily omega-3 supplementation, particularly in individuals with lower baseline omega-3 levels, noted Julian Mutz, PhD, of King’s College London, who also wasn’t involved with the study.
“These findings contribute valuable new data but given the relatively small sample size (98 participants receiving omega-3 and 95 receiving a placebo) and the sample’s composition, which is healthier than the general population, the results should be considered preliminary,” Mutz posted. “Future trials should aim to assess the generalizability of these findings, including in younger populations.”
The 777 Swiss DO-HEALTH participants had a mean baseline age of 75 years and 59% were women. About half (53%) were considered healthy agers, free of major chronic diseases, disabilities, cognitive impairments, and mental health limitations. Most participants were physically active: 29% were active one to three times a week, and 59% were active more than that. All had DNA methylation measures at baseline and 3 years.
“This study did target generally healthy adults, and we may have a conservative bias as the epigenetic analyses were performed only in the Swiss participants so far, where already at baseline over 50% were healthy agers without major chronic diseases and good physical and cognitive function,” Bischoff-Ferrari acknowledged.
The biological clocks used in the analysis have not yet been translated to clinical care as validation in major studies is largely missing, she added.
“To further advance clinical application of biological aging clocks, we plan to use DO-HEALTH as a validation platform for novel biomarkers of aging, such as protein-based biomarkers, that reflect the biological age of individual organs in still healthy adults,” she said.
Disclosures
Bischoff-Ferrari had no disclosures. One co-author reported relationships with the Epigenetic Clock Development Foundation and Altos Labs.
Partridge and Mutz reported no conflicts of interest.
Primary Source
Nature Aging
Source Reference: 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” Nat Aging 2025; DOI: 10.1038/s43587-024-00793-y.
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