Cited by 140Epigenetics and DNA MethylationGenetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and Senescence

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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Bischoff-Ferrari, Heike A., Gängler, Stephanie, Wieczorek, Maud, Belsky, Daniel W., Ryan, Joanne, Kressig, Reto W., Stähelin, Hannes B., Theiler, Robert +9 more·2025·Nature Aging

Abstract

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.
Venue
Nature Aging
Published
2025-02-03
Volume
5
Issue
3
Pages
376-385
ISSN
2662-8465 (ISSN-L)
OpenAlex
W4407088006
Cited by
140
References
67
Citations by year
2026: 90 · 2025: 50
FWCI
42.09
Type
journal article
Language
en
Open access
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

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