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Effects of Vitamin D3 Supplementation on Epigenetic Aging in Overweight and Obese African Americans With Suboptimal Vitamin D Status: A Randomized Clinical Trial
Abstract
Background: We have previously shown that vitamin D supplementation increases telomerase activity, suggesting an anti-aging effect. In this study, we aim to test the hypothesis that vitamin D supplementation would slow down epigenetic aging, a new marker of biological aging. Methods: A randomized clinical trial was previously conducted among 70 overweight/obese African Americans with serum 25-hydroxyvitamin D [25(OH)D] < 50 nmol/L, who were randomly assigned into four groups of 600 IU/d, 2,000 IU/d, 4,000 IU/d of vitamin D3 supplements or placebo followed by 16-week interventions. Whole genome-wide DNA methylation analysis was conducted in 51 participants. DNA methylation ages were calculated according to the Horvath and the Hannum methods. Methylation-based age acceleration index (∆Age) is defined as the difference between DNA methylation age and chronological age in years. Mixed-effects models were used to evaluate the treatment effects. Results: Fifty-one participants (aged 26.1 ± 9.3 years, 16% are male) were included in the study. After the adjustment of multi-covariates, vitamin D3 supplementation of 4,000 IU/d was associated with 1.85 years decrease in Horvath epigenetic aging compared with placebo (p value = .046), and 2,000 IU/d was associated with 1.90 years decrease in Hannum epigenetic aging (p value = .044). Serum 25(OH)D concentrations were significantly associated with decreased Horvath ∆Age only (p values = .002), regardless of treatments. Conclusions: Our results suggest that vitamin D supplementation may slow down Horvath epigenetic aging. But the effect on Hannum epigenetic aging is not conclusive. Large-scale and longer duration clinical trials are needed to replicate the findings.
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The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis.
“The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14–16 and contrasting with reports that biological aging may not be modifiable17.”
From Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial (2023) · cites this paper as [15]
The Discussion (page not available) reports that a randomized trial detected changes in DNA-methylation aging after vitamin D3 supplementation, supporting the broader idea that an intervention can modify a biological-aging measure. It does not report caloric restriction (CR) modifying DunedinPACE; the trial used vitamin D3 and measured epigenetic aging. (LLM, conf=0.85)
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DNA methylation age of human tissues and cell types
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Epigenetic clock analysis of diet, exercise, education, and lifestyle factors
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“85 years in overweight/obese African Americans with a serum 25-hydroxyvitamin D [25(OH)d] <50 nmol/L [31].”
BackgroundWaziry, R., Ryan, C. P., Corcoran, D. L., Huffman, K. M., Kobor, M. S., Kothari, M., Graf, G. H., Kraus, V. B., Kraus, W. E., Lin, D. T. S., et al. (2023) · Nature Aging · doi:10.1038/s43587-022-00357-y · Cited by 217
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Han, L. K. M., Verhoeven, J. E., Tyrka, A. R., Penninx, B. W. J. H., Wolkowitz, O. M., Månsson, K. N. T., Lindqvist, D., Boks, M. P., Révész, D., Mellon, S. H., et al. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2019.04.004 · Cited by 104
Responsiveness of epigenetic aging biomarkers to longevity interventions in humans
Sehgal, R., Borrus, D., Armstrong, J. F., Gonzalez, J., Kasamoto, J., Markov, Y., Priyanka, A., Smith, R., Carreras-Gallo, N., Lasky-Su, J., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04562-9 · Cited by 31
Metadata
- Authors
- Chen, L., Dong, Y., Bhagatwala, J., Raed, A., Huang, Y., & Zhu, H.
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-09-25
- Volume
- 74
- Issue
- 1
- Pages
- 91-98
- ISSN
- 1079-5006
- 1758-535X
- Cited by
- 106
- References
- 6
- Language
- en
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Funders
- American Heart Association (14GRNT20480211)
- National Institutes of Health
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