ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Clinical Diabetes
Relationship Between Vitamin D and Surrogate Parameters (Leukocyte Telomerase Length, Telomerase Activity), and Genes (ACTN3, FOXO3A, VDR, SIRT1, MSTN) for Ageing in Asian Indian with Prediabetes
Provisionally accepted
- 1Fortis C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India
- 2All India Institute of Medical Sciences New Delhi, New Delhi, India
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Vitamin D has been implicated in cellular aging through its effects on telomere maintenance, but the extent of its influence on leukocyte telomere length (LTL), telomerase activity (TA), and interactions with aging-related genetic polymorphisms remains underexplored in Asian Indians with prediabetes. This study investigated the relationship between serum vitamin D levels, LTL, TA, and variants in aging-associated genes—ACTN3, FOXO3A, VDR, SIRT1, and MSTN. A cross-sectional study was conducted among 290 prediabetic subjects (aged 20–60 years). Anthropometry, biochemical markers, LTL (by qPCR), TA (by TRAP assay), and genotyping (PCR-RFLP) were assessed. Regression analyses were used to determine independent associations, adjusted for age, sex, BMI, and fasting blood glucose. Gene-gene interactions were evaluated via Pearson correlation. Vitamin D levels showed a statistically significant but modest positive correlation with LTL (p = 0.03), which attenuated after adjustment (p = 0.06). No significant association was found between vitamin D and TA (p = 0.26). The ACTN3 polymorphism was significantly associated with TA (adjusted B = 0.10, p = 0.03). Strong gene-gene interactions were observed among SIRT1, MSTN, VDR, and FOXO3A (r = 0.56–0.82; p < 0.001), indicating a coordinated genetic influence on aging and metabolism. In Asian Indian prediabetic individuals, vitamin D exhibits only modest association with LTL, whereas a coordinated network of aging-related genes appears to exert a more substantial influence on cellular aging and metabolic risk. These preliminary findings suggest potential gene-vitamin D interactions warranting longitudinal and interventional studies for precision approaches in prediabetes management.
Keywords: ACTN3, FoxO3a, leukocyte telomere length, MSTN, SIRT1, telomerase activity, VDR
Received: 06 Nov 2025; Accepted: 28 Jan 2026.
Copyright: © 2026 Bhatt, Khurana, Pandey and Misra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Anoop Misra
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