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.
Authors
- Steve Horvath (ORCID: https://orcid.org/0000-0002-4110-3589)
- Sophie Guyonnet (ORCID: https://orcid.org/0000-0001-9527-5282)
- Stephanie Gängler (ORCID: https://orcid.org/0000-0002-7799-1514)
- Heike A. Bischoff‐Ferrari (ORCID: https://orcid.org/0000-0002-4554-658X)
- Endel John Orav (ORCID: https://orcid.org/0000-0002-8886-7252)
- Laure Rouch (ORCID: https://orcid.org/0000-0001-5992-1128)
- Maud Wieczorek (ORCID: https://orcid.org/0000-0002-4528-9923)
- Daniel W. Belsky (ORCID: https://orcid.org/0000-0001-5463-2212)
- Bruno Vellas
- Reto W. Kressig (ORCID: https://orcid.org/0000-0002-3215-7681)
- Joanne Ryan (ORCID: https://orcid.org/0000-0002-7039-6325)
- Andreas Egli (ORCID: https://orcid.org/0000-0001-5809-4167)
- René Rizzoli (ORCID: https://orcid.org/0000-0002-1537-422X)
- Walter Churchill Willett (ORCID: https://orcid.org/0000-0003-1458-7597)
- Bess Dawson‐Hughes (ORCID: https://orcid.org/0000-0003-3136-0386)
- H. B. Stähelin
- Robert Theiler
Institutions
- Tufts University (US)
- Brigham and Women's Hospital (US)
- Université Toulouse III - Paul Sabatier (FR)
- Harvard University (US)
- Inserm (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- University of Basel (CH)
- University of Zurich (CH)
- Centre Hospitalier Universitaire de Toulouse (FR)
- University Hospital of Geneva (CH)
- Jean Mayer Human Nutrition Research Center on Aging (US)
- Felix Platter-Hospital (CH)
- Hôpital Purpan (FR)
- Monash University (AU)
- Columbia University (US)
Publication Details
- Journal
- Nature Aging
- Published
- 2025-02-03
- DOI
- https://doi.org/10.1038/s43587-024-00793-y
- Citations
- 75
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 59.65
Funders
- National Science Foundation
- Pfizer
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Universität Zürich
- Nestec