However, omega-3 supplementation did not impact telomere length, a result that is at odds with data from epidemiological studies and animal research that have reported benefits of fish oil on biological age.
The VITAL study was a large, randomized, double-blind, placebo-controlled trial with older American adults. Participants were randomly assigned to receive 2,000 IU/d and/or marine n–3 FAs (1 g/d) supplements for five years.
Participants who supplement with vitamin D3 were found to have less telomere attrition and longer telomere length, with data over four years showing a 140 base pair (bp) preservation of leukocyte telomere length (LTL), which could be clinically significant, said scientists from Augusta University, Brigham and Women’s Hospital and Harvard Medical School, the Harvard T.H. Chan School of Public Health and the University of Massachusetts Lowell.
“A previous study measured absolute LTL of 510 participants in a longitudinal cohort and found an average of 460 bp decrease in LTL over 10 years,” they wrote in the American Journal of Clinical Nutrition. “Therefore, 140 bp preserved by vitamin D3 supplementation in our study could mean a 3 year decrease in aging.”
Hallmarks of aging
Telomeres, DNA sequences at the end of chromosomes that shorten as cells replicate and age, do not always correlate with chronological age, and there is evidence to suggest that telomere shortening may be modifiable by lifestyle factors.
The aging and lifespan of normal, healthy cells are linked to the so-called telomere shortening mechanism, which limits cells to a fixed number of divisions. During cell replication, the telomeres function by ensuring the cell’s chromosomes do not fuse with each other or rearrange, which can lead to cancer.
Elizabeth Blackburn, a telomere pioneer at the University of California San Francisco, likened telomeres to the ends of shoelaces, without which the lace would unravel.
With each replication, the telomeres shorten, and when the telomeres are totally consumed, the cells are destroyed (apoptosis). Telomere shortening or attrition was listed as one of the nine hallmarks of aging in a seminal paper published in Cell in 2013 by Carlos López-Otín et al. This list has since been expanded to 12 hallmarks of aging, outlined in a 2023 review by Professor López-Otín.
Nutra Healthspan Summit
The 12 Hallmarks of Aging is one of the focus themes for the inaugural Nutra Healthspan Summit, hosted by NutraIngredients, that will take place in London, Nov. 12-13, 2025. Other themes include: The ingredients – The state of the science for the key bioactives for healthspan, the microbiome and aging, the investor landscape & the disruptive start-up showcase, and skin health and aging.
Study details
The VITAL Telomere study included 1,054 older adults who had participated in the larger VITAL study. All of the VITAL Telomere study subjects were evaluated in person at the Harvard Clinical and Translational Science Center. Leukocyte telomere length (LTL) was measured at the start of the study and again after two and four years.
Results showed that vitamin D3 supplementation was associated with less shortening of telomeres and preserved telomere length over four years. Overall, the vitamin D3 supplementation group had LTLs that were approximately 35 base pairs higher per year, compared to placebo.
No effect was observed for omega-3 supplementation, added the researchers.
“Vitamin D and its receptors play an essential role in aging prevention due to its antiproliferative, anti-inflammatory and apoptotic properties,” they said. “However, the exact underlying mechanisms of preserving telomeres by vitamin D supplementation are not well understood.”
Some potential mechanisms include boosting activity of telomerase, an enzyme responsible for lengthening telomeres. Data from an earlier double-blind, randomized, and placebo-controlled clinical trial of vitamin D supplementation (equivalent to approximately 2,000 IU per day) revealed that telomerase activity increased by almost 20% over the course of the 16-week study.
Vitamin D may protect against DNA damage, said the researchers, which in turn could help preserve telomere length.
“LTL has been proposed as a potential biomarker of premature aging of the immune system, known as immunosenescence, which underlies the development of autoimmune diseases, cancer and several other chronic diseases,” the researchers noted. “Indeed, among patients with some autoimmune disease, loss of normal immune regulation and ‘premature immune senescence’ have been described. Telomere erosion appears to proceed more rapidly in subjects with autoimmune diseases.
“If telomere shortening occurs years prior to the onset of clinical autoimmune disease, there might be a window for prevention and early intervention.”
Source: The American Journal of Clinical Nutrition, doi: 10.1016/j.ajcnut.2025.05.003. “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”. Authors: H. Zhu, et al.
