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

Introduction 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. Methods 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. Results 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. Discussion 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.