Vitamin D May Slow Cellular Aging

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Vitamin D May Slow Cells’ Aging by Protecting DNA

Vitamin D supplements may help prevent the loss of telomeres, DNA sequences that shrink with aging, a large study shows. But the health effects aren’t yet clear

www.scientificamerican.com

May 21, 2025

4 min read

Vitamin D May Slow Cells’ Aging​

Vitamin D supplements may help prevent the loss of telomeres, DNA sequences that shrink with aging, a large study shows. But the health effects aren’t yet clear
By Stephanie Pappas edited by Jeanna Bryner

A new study suggests vitamin D supplements might slow cellular aging by protecting telomeres.

Olga Pankova/Getty Images
Aging
Vitamin D supplements might slow cellular aging by preventing the loss of telomeres, DNA sequences at the ends of chromosomes that shorten in old age, a new study suggests. The health effects of these findings aren’t yet clear.

Vitamin D had been touted as a panacea for a number of health conditions, from cardiovascular disease to bone loss. In 2020 a large randomized controlled trial of supplementation instead found benefits only in a few conditions, particularly autoimmune disease and advanced cases of cancer, says the new study’s co-author JoAnn Manson, a professor of medicine at Harvard Medical School and a principal investigator of that large trial, called the VITamin D and OmegA-3 TriaL (VITAL). The new study is an analysis of data from VITAL. Its finding could explain the protective effect of vitamin D supplements on these specific aging-related diseases, Manson says.


“If is replicated in another randomized trial of vitamin D supplements, I think this could translate into clinical effects for chronic diseases of aging,” she says. “We’re already seeing that vitamin D does reduce inflammation; it reduces advanced cancers and cancer deaths, as well as autoimmune diseases. This could provide a biological mechanism.”

In the VITAL project, researchers enrolled nearly 26,000 women aged 55 or older and men aged 50 or older, and they randomly assigned participants to take vitamin D supplements, fish oil supplements, a combination of both or a placebo. For the new study, published today in the American Journal of Clinical Nutrition, the scientists looked at a subset of 1,054 participants who lived close enough to Harvard’s Clinical and Translational Science Center in Boston to have their blood drawn three times over four years so researchers could measure their telomeres.


Inside the nuclei of most cells in the human body reside 46 chromosomes, where our DNA is neatly packed. Each time a cell divides, these chromosomes unravel and copy themselves, and the copies coil back into the nuclei of the new cells. Telomeres are repetitive DNA sequences that cap the ends of chromosomes. They stabilize the chromosomes during cell division, though they get shorter each time cells divide. When the telomeres get very short, the cells stop dividing and die. Over time, as more and more of our cells die, the body ages and ultimately stops functioning. Telomeres aren’t a perfect clock for health—very long telomeres can increase cancer risk by stabilizing mutated cells—but they’re often used as a biomarker for aging.

Participants in the placebo and supplement groups had similar telomere lengths at the beginning of the study, the researchers found. But over the four years of follow-up, people assigned to take 2,000 international units of vitamin D per day showed less shortening of their telomeres compared with people in the placebo group. Fish oil had no significant effect.

 

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The Relationship Between Vitamin D and Telomere/Telomerase: A Comprehensive Review - PubMed

Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Evidences from various organisms suggests that several factors influence telomere length regulation, such as telomere binding proteins...

pubmed.ncbi.nlm.nih.gov

The Relationship Between Vitamin D and Telomere/Telomerase: A Comprehensive Review​

M Zarei <a title="Mohammad Hassan Javanbakht, Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran, Email: [email protected]." href="The Relationship Between Vitamin D and Telomere/Telomerase: A Comprehensive Review - PubMed">1</a>, M Zarezadeh, F Hamedi Kalajahi, M H Javanbakht
Affiliations Expand

• PMID: 33331615
• DOI: 10.14283/jfa.2020.33

Abstract​

Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Evidences from various organisms suggests that several factors influence telomere length regulation, such as telomere binding proteins, telomere capping proteins, telomerase, and DNA replication enzymes. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. In this study, our main goal is investigating the relationship between telomerase enzyme and vitamin D. Findings of this study suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases. Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. Significant Low levels of telomerase activity create short telomeres, which in turn signal exit from the cell cycle resulting in cell senescence and apoptosis. In follow-up examination, the patients who remained vitamin D deficient tended to have shorter telomeres than those patients whose 25-hydroxyvitamin D levels were depleted. Increasing 25-hydroxyvitamin D levels in patients with SLE may be beneficial in maintaining telomere length and preventing cellular aging. Moreover, anti-telomere antibody levels may be a promising biomarker of SLE status and disease activity.

 

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https://www.sciencedirect.com/science/article/abs/pii/S0002916525002552?via%3Dihub

Vitamin D3 and marine ω-3 fatty acids supplementation and leukocyte telomere length: 4-year findings from the VITamin D and OmegA-3 TriaL (VITAL) randomized controlled trial​

Author links open overlay panelHaidong Zhu 1, JoAnn E Manson 2 3, Nancy R Cook 2 3, Bayu B Bekele 1, Li Chen 1, Kevin J Kane 4, Ying Huang 1, Wenjun Li 4, William Christen 2, I-Min Lee 2 3, Yanbin Dong 1
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Abstract​

Background​

Limited studies suggest that vitamin D or omega 3 fatty acids (n-3 FAs) supplementation may be beneficial for telomere maintenance, however, evidence from large randomized clinical trial is lacking.

Objective​

We aimed to determine whether vitamin D or n-3 FAs supplementation reduce leukocyte telomere length (LTL) attrition over time by leveraging the VITamin D and OmegA-3 TriaL (VITAL) trial.

Methods​

VITAL is a large, randomized, double-blind, placebo-controlled tr ial with a 2 x 2 factorial design of vitamin D3 (2,000 IU/day) and marine n-3 FAs (1 g/day) supplements for 5 years among a representative sample of 25,871 US females ≥55 and males ≥50 years of age. The VITAL Telomere study (NCT04386577) included 1054 participants who were evaluated in person at the Harvard Clinical and Translational Science Center. LTL was determined by the Absolute Human Telomere Length Quantification quantitative Polymerase Chain Reaction (PCR) method at baseline, Year 2, and Year 4. The pre-specified primary outcome measures were changes in LTL between baseline, Year 2 and Year 4. Analyses of intervention effect used mixed-effects linear regression models.

Results​

LTL was measured in a total of 2,571 samples from the 1031 participants at baseline, year 2, and year 4. Compared to placebo, vitamin D3 supplementation significantly decreased LTL attrition by 0.14 kilo base pairs (kb) (95%CI: 0.007, 0.27) over 4 years (p = 0.039). Overall trend analysis showed that the vitamin D3 supplementation group had LTLs that were about 0.035 kb higher per year of follow-up compared to placebo group (95%CI: 0.002, 0.07, p=0.037). Marine n-3 FAs supplementation had no significant effect on LTL at either year 2 or year 4.

Conclusion​

4-years of supplementation with 2000 IU/day vitamin D3 reduced telomere attrition by 140 bp, suggesting that vitamin D3 daily supplementation with or without n-3 FAs might have a role in counteracting telomere erosion or cell senescence.

Introduction​

Telomeres, specialized chromatin structures located at the chromosomal ends, protect chromosome integrity and stability. Telomeres naturally shorten with every cell cycle, and cells with critically short telomeres undergo replicative senescence and apoptosis [1].
Telomere shortening has been proposed as a mechanism for decreasing chromosomal stability, which increases risks for chronic diseases, cancer, cardiovascular disease, and overall mortality [1,2]. Leukocyte telomere length (LTL) represents a key integrating component of genetic factors and the cumulative effects of environmental, lifestyle, and nutritional factors throughout human life. Therefore, it is crucial to identify the factors that can slow down telomere shortening, which in turn could prevent premature aging or age-related diseases.
Both vitamin D and omega-3 fatty acids [n–3 (ω-3) FAs] are important for a range of vital cellular processes, including cellular differentiation, proliferation, and apoptosis, and have been postulated to be protective for aging and age-related chronic diseases. Associations between telomere length and vitamin D concentrations [[3], [4], [5]] or n–3 FAs [[6], [7], [8], [9])] have been reported in cross-sectional studies. A few short-term small-scale intervention studies with 8 wk to 12 mo supplementation of vitamin D [[10], [11], [12]] and n–3 FAs [13] showed beneficial effects on telomere length or telomerase activity. However, a recent review concluded that the results of the studies performed to date are inconsistent [14]. Moreover, large randomized controlled trials with longer treatment duration remain scarce.
The VITamin D and OmegA-3 TriaL (VITAL) is a completed large, randomized, double-blind, placebo-controlled trial with a 2 × 2 factorial design of vitamin D3 (2000 IU/d) and marine n–3 FAs (1 g/d) supplements for 5 y among a representative sample of 25,871 US females aged ≥55 and males aged ≥50 y. Autoimmune diseases, characterized by an inflammatory autoimmune response to self-tissues, and cancer are 2 chronic diseases that increase in prevalence with age. In the VITAL trial, compared with placebo, daily supplementation with 2000 IU/d vitamin D, but not n–3 FAs, reduced the incidence of advanced (metastatic or fatal) cancer by 17% [15]. Moreover, supplementation with vitamin D with or without marine n–3 FAs for 5 y reduced all incident autoimmune diseases by 22%, whereas n–3 FAs supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant) [16]. Furthermore, our VITAL ancillary study (NCT04386577) found that supplementation of vitamin D3 with or without n–3 FA decreased circulating high sensitivity-C-reactive protein concentrations by 19% at year 2 [17]. As such, we tested whether long-term vitamin D3 or n–3 FAs supplementation reduced LTL attrition in VITAL.

Section snippets​

Study population and design​

The VITAL study design, baseline characteristics, and main results have been published previously [[18], [19], [20], [21]]. In brief, VITAL was a completed nationwide, randomized, double-blind, placebo-controlled trial of the benefits and risks of supplemental vitamin D3 (2000 IU/d) and marine n–3 FAs (1 g/d Omacor fish-oil capsule with 840 mg n–3 FAs, including EPA, 460 mg + DHA, 380 mg) in the primary prevention of cancer and cardiovascular disease among 25,871 US males and females, aged ≥50

General characteristics of the participants​

A total of 2571 LTL measurements (993 from baseline, 918 from year 2, and 660 from year 4) from 1031 participants (aged 64.9 ± 6.5 y, 49% female, 84% White, and 9% Black) were included in this study (Figure 1). Table 1 presents the baseline characteristics according to vitamin D3 and marine n–3 FAs assignments. There was no significant difference in the baseline general characteristics between the vitamin D3 active group and vitamin D3 placebo group or between the marine n–3 FAs active group

Discussion​

In the VITAL-CTSC subcohort, we found that vitamin D3 supplementation significantly reduced telomere attrition over a 4-y period, preventing 140 bp of LTL loss compared with placebo. Overall trend analysis also showed that vitamin D3 supplementation group had LTLs that were ∼0.035 kb higher per year of follow-up compared with placebo group, which equates to 140 bp over the 4-y period. However, we did not observe any significant effect of n–3 FAs on LTL either at year 2 or year 4 or in overall

Author contribution​

The authors’ responsibilities were as follows – YD, HZ, NC, JM: designed research; YH and HZ: conducted research; WC, JM: provided essential reagents or provided essential materials; YH, HZ: performed LTL analysis; BBB, LC, KK, NC, WL: analyzed data or performed statistical analysis; YD, LC, HZ: drafted paper; JM, NC, WC, BBB, IML: revised paper. HZ, YD, JM are responsible for design, writing and final content; and all authors: have read and approved the final version of the manuscript.

Data availability​

Data described in the manuscript, code book, and analytic code will be made available upon request.

Funding​

This work was supported by R01 HL131674 to YD, HZ and JM from the National Heart, Lung, and Blood Institute. The parent VITAL trial is supported by R01 CA138962 from The National Cancer Institute and R01 AT011729 from the National Center for Complementary and Integrative Health. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report as well as in the decision to submit the paper for publication.

Conflict of interest​

The authors report no conflicts of interest.

 

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IMO, Vitamin D plus k2 is worthwhile just for the benefits to the innate immune system alone. Everything else is a nice bonus. Above 50 is apparently the sweet spot. Pneumonia is a fairly big risk for may of us.