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
While observational studies and small pilot trials suggest that vitamin D, omega-3 and exercise may slow biological aging, larger clinical trials testing these treatments individually or in combination are lacking. Here, we report the results of a post hoc analysis among 777 participants of the DO-HEALTH trial on the effect of vitamin D (2,000 IU per day) and/or omega-3 (1 g per day) and/or a home exercise program on four next-generation DNA methylation (DNAm) measures of biological aging (PhenoAge, GrimAge, GrimAge2 and DunedinPACE) over 3 years. Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2 and DunedinPACE, and all three treatments had additive benefits on PhenoAge. Overall, from baseline to year 3, standardized effects ranged from 0.16 to 0.32 units (2.9–3.8 months). In summary, our trial indicates a small protective effect of omega-3 treatment on slowing biological aging over 3 years across several clocks, with an additive protective effect of omega-3, vitamin D and exercise based on PhenoAge.
AI attempt at summarizing the video and some related sources:
Higher levels of omega-3 fatty acids, particularly EPA and DHA found in marine sources, are consistently associated with increased life expectancy and reduced mortality risk. Observational studies involving over 160,000 participants show those with the highest blood levels of omega-3s have a 17–21% lower risk of all-cause mortality and up to a 5-year increase in life expectancy compared to those with the lowest levels[3][4][23][25]. This benefit is comparable to quitting smoking, which reduces life expectancy by ~4.7 years[3][28].
Key Findings:
Cardiovascular and cancer mortality: High omega-3 levels correlate with 21% lower cardiovascular mortality and 19% lower cancer-related mortality[4][20].
Omega-3 Index: An index ≥8% (common in populations like Japan) is linked to a 5-year survival advantage over those with ≤4% (typical in the U.S.)[2][4][23].
Synergy with lifestyle: Non-smokers with high omega-3 levels have the longest survival, while smokers with low omega-3 levels fare worst[5][24].
Mechanisms and Recommendations:
Anti-inflammatory effects: Omega-3s reduce chronic inflammation and support specialized pro-resolving mediators (SPMs), which resolve inflammation[1][25].
Dietary intake: Consuming 1,000 mg/day of EPA+DHA from fatty fish (e.g., salmon, sardines) or supplements is advised to achieve optimal blood levels[4][17].
Limitations and Considerations:
While observational data show strong correlations, causation isn’t proven. Randomized trials are needed[4][13].
Supplements are effective but dietary sources provide additional nutrients[8][18].
In summary, optimizing omega-3 intake through diet or supplementation may significantly enhance longevity, particularly when combined with healthy lifestyle choices.