Skip to main content

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


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.

This is a preview of subscription content, access via your institution.

Figure 1


  1. 1.

    Aubert G, Lansdorp PM. Telomeres and Aging. Physiological Reviews. 2008;88(2):SS7–79.

    Google Scholar 

  2. 2.

    Pusceddu I, Farrell Christopher-John L, Di Pierro Angela M, Jani E, Herrmann W, Herrmann M. The role of telomeres and vitamin D in cellular aging and age-related diseases. Clinical Chemistry and Laboratory Medicine (CCLM)2015. p. 1661.

  3. 3.

    Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB. Telomere end-replication problem and cell aging. Journal of Molecular Biology. 1992;225(4):951–60.

    PubMed  CAS  Google Scholar 

  4. 4.

    Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;34S:4S8.

    Google Scholar 

  5. 5.

    Zhang J, Rane G, Dai X, Shanmugam MK, Arfuso F, Samy RP, Lai MK, Kappei D, Kumar AP, Sethi G. Ageing and the telomere connection: An intimate relationship with inflammation. Ageing Res Rev. 2016;25:55–69.

    PubMed  CAS  Google Scholar 

  6. 6.

    Kord-Varkaneh H, Kord-Varkaneh H, Rinaldi G, Hekmatdoost A, Fatahi S, Tan SC, Shadnoush M, Khani V, Mousavi SM, Zarezadeh M. The influence of vitamin D supplementation on IGF-1 levels in humans: A systematic review and meta-analysis. 2020.

  7. 7.

    Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proceedings of the National Academy of Sciences. 2006; 103(47): 17589–94.

    CAS  Google Scholar 

  8. 8.

    Cong Y-S, Wright WE, Shay JW. Human Telomerase and Its Regulation. Microbiology and Molecular Biology Reviews. 2002;66(3):407–25.

    PubMed  PubMed Central  CAS  Google Scholar 

  9. 9.

    Harley CB, Vaziri H, Counter CM, Allsopp RC. The telomere hypothesis of cellular aging. Experimental Gerontology. 1992;27(4):375–82.

    PubMed  CAS  Google Scholar 

  10. 10.

    Olovnikov AM. A theory of marginotomy: The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. Journal of Theoretical Biology. 1973;41(l):181–90.

    PubMed  CAS  Google Scholar 

  11. 11.

    Blackburn EH. Structure and function of telomeres. Nature. 1991;350:569.

    PubMed  CAS  Google Scholar 

  12. 12.

    Morin GB. Is Telomerase a Universal Cancer Target? JNCI: Journal of the National Cancer Institute. 1995;87(12):859–61.

    PubMed  CAS  Google Scholar 

  13. 13.

    Greider CW, Blackburn EH. Telomeres, telomerase and cancer. Sci Am. 1996;274(2):92–7.

    PubMed  CAS  Google Scholar 

  14. 14.

    Wai LK. Telomeres, telomerase, and tumorigenesis—a review. MedGenMed. 2004;6(3):19.

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Gravel S, Wellinger RJ. Maintenance of double-stranded telomeric repeats as the critical determinant for cell viability in yeast cells lacking Ku. Mol Cell Biol. 2002;22(7):2182–93.

    PubMed  PubMed Central  CAS  Google Scholar 

  16. 16.

    Chan SS, Chang S. Defending the end zone: Studying the players involved in protecting chromosome ends. FEBS Letters. 2010;584(17):3773–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  17. 17.

    Zhu H, Shuman S. Gap filling activities of Pseudomonas DNA ligase D (LigD) polymerase and functional interactions of LigD with the DNA end-binding Ku protein. J Biol Chem. 2010;285(7):4815–25.

    PubMed  CAS  Google Scholar 

  18. 18.

    Mostafa WZ, Hegazy RA. Vitamin D and the skin: Focus on a complex relationship: A review. J Adv Res. 2015;6(6):793–804.

    PubMed  CAS  Google Scholar 

  19. 19.

    Lu Z, Chen TC, Zhang A, Persons KS, Kohn N, Berkowitz R, Martinello S, Holick MF. An evaluation of the vitamin D3 content in fish: Is the vitamin D content adequate to satisfy the dietary requirement for vitamin D? J Steroid Biochem Mol Biol. 2007;103(3–5):642–4.

    PubMed  PubMed Central  CAS  Google Scholar 

  20. 20.

    Chatterjea M, Shinde R. Textbook of Medical Biochemistry: Eighth Edition: Jaypee Brothers, Medical Publishers Pvt. Limited; 2011.

  21. 21.

    Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. The American Journal of Clinical Nutrition. 2008;88(2):491S–9S.

    PubMed  CAS  Google Scholar 

  22. 22.

    Cashman KD. Vitamin D in childhood and adolescence. Postgrad Med J. 2007;83(978):230–5.

    PubMed  PubMed Central  CAS  Google Scholar 

  23. 23.

    Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319–29.

    PubMed  PubMed Central  CAS  Google Scholar 

  24. 24.

    Matyjaszek-Matuszek B, Lenart-Lipinska M, Wozniakowska E. Clinical implications of vitamin D deficiency. Prz Menopauzalny. 2015; 14(2):75–81.

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Cherniack EP, Troen BR, Florez HJ, Roos BA, Levis S. Some new food for thought: the role of vitamin D in the mental health of older adults. Curr Psychiatry Rep. 2009; 11(1): 12–9.

    PubMed  Google Scholar 

  26. 26.

    Jacobs ET, Kohler LN, Kunihiro AG, Jurutka PW. Vitamin D and Colorectal, Breast, and Prostate Cancers: A Review of the Epidemiological Evidence. J Cancer. 2016;7(3):232–40.

    PubMed  PubMed Central  CAS  Google Scholar 

  27. 27.

    Myhr K-M. Vitamin D treatment in multiple sclerosis2009. 104–8 p.

  28. 28.

    McGrath J, Saari K, Hakko H, Jokelainen J, Jones P, Jarvelin MR, Chant D, Isohanni M. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophr Res. 2004;67(2–3):237–45.

    PubMed  Google Scholar 

  29. 29.

    Salahuddin N, Ali F, Hasan Z, Rao N, Aqeel M, Mahmood F. Vitamin D accelerates clinical recovery from tuberculosis: results of the SUCCINCT Study [Supplementary Cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis’. BMC Infectious Diseases. 2013;13(1):22.

    PubMed  PubMed Central  CAS  Google Scholar 

  30. 30.

    Herrmann M, Sullivan DR, Veillard AS, McCorquodale T, Straub TR, Scott R, Laakso M, Topliss D, Jenkins AJ, Blankenberg S, et al. Serum 25-hydroxyvitamin D: a predictor of macrovascular and microvascular complications in patients with type 2 diabetes. Diabetes Care. 2015;38(3):521–8.

    PubMed  CAS  Google Scholar 

  31. 31.

    Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, Mullie P, Autier P. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011;128(6):1414–24.

    PubMed  CAS  Google Scholar 

  32. 32.

    Trivedi DP, Doll R, Khaw KT. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326(7387):469.

    PubMed  PubMed Central  CAS  Google Scholar 

  33. 33.

    Richards JB, Valdes AM, Gardner JP, Paximadas D, Kimura M, Nessa A, Lu X, Surdulescu GL, Swaminathan R, Spector TD, et al. Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women. Am J ClinNutr. 2007;86(5): 1420–5.

    CAS  Google Scholar 

  34. 34.

    Liu JJ, Prescott J, Giovannucci E, Hankinson SE, Rosner B, Han J, De Vivo I. Plasma vitamin D biomarkers and leukocyte telomere length. Am J Epidemiol. 2013;177(12):1411–7.

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Hoffecker BM, Raffield LM, Kamen DL, Nowling TK. Systemic lupus erythematosus and vitamin D deficiency are associated with shorter telomere length among African Americans: a case-control study. PLoS One. 2013;8(5).

    Google Scholar 

  36. 36.

    Kim JH, Kim GJ, Lee D, Ko JH, Lim I, Bang H, Koes BW, Seong B, Lee DC. Higher maternal vitamin D concentrations are associated with longer leukocyte telomeres in newborns. Matern Child Nutr. 2018; 14(1).

    Google Scholar 

  37. 37.

    Lau H, M.L AF, Ludin M, Rajab N, Shahar S. Identification of Neuroprotective Factors Associated with Successful Ageing and Risk of Cognitive Impairment among Malaysia Older Adults. Current Gerontology and Geriatrics Research. 2017;2017:1–7.

    Google Scholar 

  38. 38.

    Schottker B, Hagen L, Zhang Y, Gao X, Holleczek B, Gao X, Brenner H. Serum 25-Hydroxyvitamin D Levels as an Aging Marker: Strong Associations With Age and All-Cause Mortality Independent From Telomere Length, Epigenetic Age Acceleration, and 8-Isoprostane Levels. J Gerontol A Biol Sei Med Sci. 2019;74(1): 121–8.

    Google Scholar 

  39. 39.

    Herlin M, Broberg K, Igra AM, Li H, Harari F, Vahter M. Exploring telomere length in mother-newborn pairs in relation to exposure to multiple toxic metals and potential modifying effects by nutritional factors. BMC Med. 2019;17(1):77.

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    Zhu H, Guo D, Li K, Pedersen-White J, Stallmann-Jorgensen IS, Huang Y, Parikh S, Liu K, Dong Y. Increased telomerase activity and vitamin D supplementation in overweight African Americans. Int J Obes (Lond). 2012;36(6):805–9.

    CAS  Google Scholar 

  41. 41.

    Borras M, Panizo S, Sarro F, Valdivielso JM, Fernandez E. Assessment of the potential role of active vitamin D treatment in telomere length: a case-control study in hemodialysis patients. ClinTher. 2012;34(4):849–56.

    CAS  Google Scholar 

  42. 42.

    Siebert C, Dos Santos TM, Berto CG, Parisi MM, Coelho RP, Manfredini V, Barbe-Tuana FM, Wyse ATS. Vitamin D Supplementation Reverses DNA Damage and Telomeres Shortening Caused by Ovariectomy in Hippocampus of Wistar Rats. NeurotoxRes. 2018;34(3):538–46.

    CAS  Google Scholar 

  43. 43.

    Lanske B, Razzaque MS. Vitamin D and aging: old concepts and new insights. J Nutr Biochem. 2007;18(12):771–7.

    PubMed  PubMed Central  CAS  Google Scholar 

  44. 44.

    Keisala T, Minasyan A, Lou Y-R, Zou J, Kalueff A, Pyykkö I, Tuohimaa P. Premature aging in vitamin D receptor mutant mice2009. 91–7 p.

  45. 45.

    Valcheva P, Cardus A, Panizo S, Parisi E, Bozic Stanojevic M, Lopez-Novoa J, Dusso A, Fernández E, Valdivielso J. Lack of vitamin D receptor causes stress-induced premature senescence in vascular smooth muscle cells through enhanced local angiotensin-II signals2014. 247–55 p.

  46. 46.

    Nakatani T, Sarraj B, Ohnishi M, Densmore MJ, Taguchi T, Goetz R, Mohammadi M, Lanske B, Razzaque MS. In vivo genetic evidence for klotho-dependent, fibroblast growth factor 23 (Fgf23) -mediated regulation of systemic phosphate homeostasis. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2009;23(2):433–41.

    CAS  Google Scholar 

  47. 47.

    Lanske B, Razzaque MS. Premature aging in klotho mutant mice: cause or consequence? Ageing research reviews. 2007;6(l):73–9.

    PubMed  PubMed Central  Google Scholar 

  48. 48.

    Davis CD, Milner JA. Nutrigenomics, vitamin D and cancer prevention. J Nutrigenet Nutrigenomics. 2011;4(1):1–11.

    PubMed  PubMed Central  CAS  Google Scholar 

  49. 49.

    Kang SN, Kim SH, Chung SW, Lee MH, Kim HJ, Kim TS. Enhancement of 1 alpha, 25-dihydroxyvitamin D(3)-induced differentiation of human leukaemia HL-60 cells into monocytes by parthenolide via inhibition of NF-kappa B activity. British journal of pharmacology. 2002; 135(5): 1235–44.

    PubMed  PubMed Central  CAS  Google Scholar 

  50. 50.

    Ikeda N, Uemura H, Ishiguro H, Hori M, Hosaka M, Kyo S, Miyamoto K, Takeda E, Kubota Y. Combination treatment with lalpha,25-dihydroxyvitamin D3 and 9-cis-retinoic acid directly inhibits human telomerase reverse transcriptase transcription in prostate cancer cells. Mol Cancer Ther. 2003;2(8):739–46.

    PubMed  CAS  Google Scholar 

  51. 51.

    Kasiappan R, Shen Z, Tse AKW, Jinwal U, Tang J, Lungchukiet P, Sun Y, Kruk P, Nicosia SV, Zhang X, et al. 1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498. The Journal of biological chemistry. 2012;287(49):41297–309.

    PubMed  PubMed Central  CAS  Google Scholar 

  52. 52.

    Querfeld U. Vitamin D and inflammation. Pediatric Nephrology. 2013;28(4):605–10.

    PubMed  Google Scholar 

  53. 53.

    Gorman S, Geldenhuys S, Judge M, Weeden C, Waithman J, Hart P. Dietary Vitamin D Increases Percentages and Function of Regulatory T Cells in the Skin-Draining Lymph Nodes and Suppresses Dermal Inflammation. Journal of Immunology Research. 2016;2016:1–13.

    Google Scholar 

Download references

Author information



Corresponding authors

Correspondence to Meysam Zarezadeh or Mohammad Hassan Javanbakht.

Additional information

Conflicts of Interest: The authors have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zarei, M., Zarezadeh, M., Hamedi Kalajahi, F. et al. The Relationship Between Vitamin D and Telomere/Telomerase: A Comprehensive Review. J Frailty Aging 10, 2–9 (2021).

Download citation

Key words

  • Vitamin D
  • telomere
  • telomerase