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
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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.
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Adjunctive anti-inflammatory agents such as omega-3 fatty acids or low-dose acetylsalicylic acid can help mitigate chronic low-grade inflammation commonly associated with aging and metabolic dysfunction, but evidence is still very limited.
“Adjunctive anti-inflammatory agents such as omega-3 fatty acids or low-dose acetylsalicylic acid (AAS) can also help to mitigate the chronic low-grade inflammation commonly associated with aging and metabolic dysfunction, but evidence is still very limited”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [124]
The Main section reports that omega-3 changed DNA-methylation-based aging markers, including some associated with metabolic dysregulation. It does not establish that omega-3 mitigates chronic low-grade inflammation, and the passages found when searching for inflammation and low-dose acetylsalicylic acid do not address that treatment or the claim that evidence for it is limited. No page numbers are available in our copy. (LLM, conf=0.72)
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- Authors
- Bischoff-Ferrari, H. A., Gängler, S., Wieczorek, M., Belsky, D. W., Ryan, J., Kressig, R. W., Stähelin, H. B., Theiler, R., Dawson-Hughes, B., Rizzoli, R., Vellas, B., Rouch, L., Guyonnet, S., Egli, A., Orav, E. J., Willett, W., & Horvath, S.
- Affiliations
- University of Basel (CH)
- Columbia University (US)
- Monash University (AU)
- University of Zurich (CH)
- University of Geneva (CH)
- Université Toulouse III - Paul Sabatier (FR)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Altos Labs (US)
- Corresponding author
- Bischoff-Ferrari, Heike A.
- ORCID
- Venue
- Nature Aging
- Published
- 2025-02-03
- Volume
- 5
- Issue
- 3
- Pages
- 376-385
- ISSN
- 2662-8465 (ISSN-L)
- PMC
- PMC11922767
- OpenAlex
- W4407088006
- Cited by
- 140
- References
- 67
- Citations by year
- 2026: 90 · 2025: 50
- FWCI
- 42.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Pfizer
- European Commission (278588)
- Agence Nationale de la Recherche (ANR-23-IAHU-0011)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (204452)
- Universität Zürich
- Nestec
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- biological aging, DNA methylation clocks, vitamin D supplementation, omega-3 fatty acids, home-based exercise, PhenoAge, GrimAge, DunedinPACE, additive effects, older adults, epigenetic aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Female, Humans, Male, Middle Aged, Vitamin D, Exercise, Fatty Acids, Omega-3, DNA Methylation, Dietary Supplements
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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