Omega-3 and longevity: a link confirmed by years of research

A healthy lifestyle can make us live longer. But what are the ingredients of this lifestyle? When the spotlight is shone on nutrition, Omega-3 polyunsaturated fats emerge among the elixirs of youth. The mechanisms behind their benefits have not yet been fully elucidated, but their link to longevity is now confirmed by years of research. Here's what the available data tell us.

Omega-3 and longevity - but also quality - of life: this is the pair resulting from the meta-analysis published in Nature Communications in 2021 by an international group of researchers, including experts from Harvard and Cambridge Universities. To definitively answer the question of whether there is a relationship between PolyUnsaturated Fatty Acids (PUFAs) and longevity, the publication's authors analyzed, using careful statistical methods, data on 42,500 people involved in 17 different clinical trials. They found that the risk of dying was significantly lower for people with the highest levels of omega-3 fatty acids in their blood.

Years of research on Omega-3s

Fats belonging to the Omega-3 family have been the subject of much investigation since their association with a lower incidence of cardiovascular problems among Greenlandic Eskimo populations was observed in the 1970s. Although many studies have been done on the subject since then, there has always been much debate about the results obtained. 

This situation is far from uncommon when dealing with studies in the field of nutrition, because of the heterogeneity of the samples studied, the difficulty in analyzing results years later, uncertainty in measurements, and effects that can take a long time to manifest themselves and are, therefore, difficult to monitor. 

The latter is precisely the case with the effects of what we eat or specific components of food on longevity. Indeed, to assess the impact on lifespan, it is necessary to follow study participants and monitor their eating habits-and, more generally, their lifestyles-for decades; added to this complexity is the need to have a very large and as homogeneous sample as possible. 

For these reasons, meta-analysis, a research tool that, by summarizing data from different studies, provides a broader view of the phenomenon and greater statistical power, is used extensively in studies of the effects of diet on health. 

Regarding Omega-3 studies, prior to the publication that appeared in the pages of Nature Communication, the only meta-analyses conducted to assess a possible association with mortality reduction had been based on self-reported nutrient intakes, which for a variety of reasons leads to too rough an estimate of actual nutrient intakes: 

- fish (which is the main dietary source of long-chain Omega-3s EPA - eicosapentaenoic acid - and DHA - docosahexaenoic acid) contains many nutrients in addition to Omega-3s, any of which could have an impact on longevity;
- self-reported food intake depends on memory, which is not always reliable;
- databases used to estimate nutrient intake based on food consumption may be outdated.

Omega-3 in the blood

A more reliable and objective measure of Omega-3 consumption is their level in the blood, which depends primarily on precisely the dietary intake of these fatty acids. The researchers in the publication that appeared in Nature Communications looked at 17 studies in which the association between these levels and all-cause mortality had been evaluated; in total, data from 42,500 people followed for an average time of 16 years were analyzed. 

The mean age of the subjects at the start of the studies was 65 years, with a range of 50 to 81 years. Thirty-seven percent of the sample died during follow-up; about 30 percent of the deaths were attributed to cardiovascular disease, 30 percent to cancer, and the remaining 39 percent to all other causes.

Those who live longer have more omega-3s in their system

Analyzing all the available data and after due consideration of the possible effect of other important risk factors, it was found that long-chain Omega-3 fatty acids (PUFA LC n-3) were associated with a lower risk of mortality. Specifically, it was found that the 20% of people with the highest Omega-3 levels had run about a 15-18% lower risk of dying than the 20% of people with the lowest levels; the associations were linear for both DHA and total EPA+DHA, and for another Omega-3, DPA (docosapentaenoic acid). This suggests that maintaining high Omega-3 levels in tissues may slow the aging process. 

The mechanisms underlying the beneficial effect of n-3 LC PUFAs on human biology are diverse, including:

- Lowering of blood triglycerides;
- antihypertensive effect;
- promotion of proper functioning of the heart and brain;
- prevention of platelet aggregation and reduction of the risk of thrombus formation;
- anti-inflammatory action;
- positive effects on the biology of adipocytes (the cells of fat tissue).

There is also no shortage of evidence for a possible protective effect of Omega-3 on telomeres, the molecular "caps" that protect compacted DNA in the cell nucleus. In a 2013 paper published in Brain, Behaviour, and Immunity, Janice Kiecolt-Glaser and colleagues associated reduced Omega-6/Omega-3 ratios with longer telomeres, suggesting an impact of this ratio on cellular aging.

More recently, in 2025, Heike Bischoff-Ferrari and colleagues associated taking a supplemental dose of Omega-3 with three "molecular clocks" used to measure biological aging based on DNA methylation, an epigenetic modification of DNA-that is, one that does not change the sequence of the genetic material, but can affect how it functions.

Omega-3 supplementation and DNA methylation.

The research team led by Bischoff-Ferrari looked at data from 777 individuals involved in DO-HEALTH, a multicenter, randomized, controlled trial that recruited adults aged 70 years and older in 5 European countries. Some participants took 1 gram of Omega-3 daily, alone or in combination with vitamin D, exercise, or both, for 3 years; blood samples were collected at the beginning of the study and after 1, 2, and 3 years from which DNA was extracted.

In the case of participants recruited in Switzerland, DNA extracted from blood samples collected 3 years after the start of the study was analyzed for methylation. The average age of these participants at the start of the study was 75 years; 59% were women. And it was from these participants that individuals were selected for the analysis conducted by Bischoff-Ferrari and colleagues.

Compared with what was observed in the control group, daily intake of Omega-3 was associated with slowing down aging assessed on the basis of 3 of the 4 molecular clocks used by the researchers. In the case of one of these molecular clocks, the effect was greater if, in addition to taking Omega-3, the participants had also taken vitamin D or done physical activity, or if they had been instructed to take Omega-3 plus vitamin D and do physical activity.

"Previously, in the DO-HEALTH study, we had observed that Omega-3 alone reduced the rate of infections by 13 percent and the rate of falls by 10 percent, and that all 3 interventions combined [Omega-3, vitamin D, and physical activity, ed.] showed a significant beneficial effect by reducing pre-fragility by 39 percent and the incidence of invasive cancer by 61 percent," Bischoff-Ferrari and colleagues write in the pages of Nature Aging. "The purpose of the DNA methylation analysis was to test the effects of interventions at the molecular level. Three of the four DNA methylation measurements showed the clearest signal for Omega-3, highlighting a specific and relevant epigenetic response. This specificity is encouraging and supports the idea that targeted nutritional strategies may have specific epigenetic effects on aging."

Toward personalized recruitment

Commenting on the results of their analysis, Bischoff-Ferrari and colleagues also highlighted the presence of larger epigenetic effects in people with lower baseline Omega-3 levels. This, the researchers point out, "further reinforces the need for personalized approaches" and "suggests that baseline nutritional status might influence the magnitude of the epigenetic response, emphasizing the potential of Omega-3s as a targeted intervention to influence (...) biological age." Moreover, as suggested by these and other studies, the combination with vitamin D and physical activity could further enhance the effect of Omega-3 supplementation on longevity.

But, as pointed out by the authors of the meta-analysis published in Nature Communication, "regardless of their specific actions," and although many mechanisms underlying their action remain to be elucidated, it seems clear that "higher cellular levels of Omega-3 appear, in general, to slow the aging process." 

Bibliographic references:

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Harris WS, Tintle NL, Imamura F, Qian F, Korat AVA, Marklund M, Djoussé L, Bassett JK, Carmichael PH, Chen YY, Hirakawa Y, Küpers LK, Laguzzi F, Lankinen M, Murphy RA, Samieri C, Senn MK, Shi P, Virtanen JK, Brouwer IA, Chien KL, Eiriksdottir G, Forouhi NG, Geleijnse JM, Giles GG, Gudnason V, Helmer C, Hodge A, Jackson R, Khaw KT, Laakso M, Lai H, Laurin D, Leander K, Lindsay J, Micha R, Mursu J, Ninomiya T, Post W, Psaty BM, Risérus U, Robinson JG, Shadyab AH, Snetselaar L, Sala-Vila A, Sun Y, Steffen LM, Tsai MY, Wareham NJ, Wood AC, Wu JHY, Hu F, Sun Q, Siscovick DS, Lemaitre RN, Mozaffarian D; Fatty Acids and Outcomes Research Consortium (FORCE). Blood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies. Nat Commun. 2021 Apr 22;12(1):2329. doi: 10.1038/s41467-021-22370-2

Kiecolt-Glaser JK, Epel ES, Belury MA, Andridge R, Lin J, Glaser R, Malarkey WB, Hwang BS, Blackburn E. Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial. Brain Behav Immun. 2013 Feb;28:16-24. doi: 10.1016/j.bbi.2012.09.004