Epigenetic Clock and Leukocyte Telomere Length Are Associated with Vitamin D Status but not with Functional Assessments and Frailty in the Berlin Aging Study II

Abstract

DNA methylation (DNAm) age acceleration, a parameter derived via the epigenetic clock, has recently been suggested as a biomarker of aging. We hypothesized that accelerated biological aging, measured by both this new and the established biomarker of aging, relative leukocyte telomere length (rLTL), are associated with vitamin D deficiency. Moreover, we tested for an association between rLTL/DNAm age acceleration and different clinical assessments for functional capacity, including the Fried frailty score. Cross-sectional data of 1,649 participants of the Berlin Aging Study II was available (~50% female, age: 22-37 and 60-84 years). A seven cytosine-phosphate-guanine clock was estimated to calculate the DNAm age acceleration. rLTL was measured by quantitative real-time polymerase chain reaction (PCR). 25-hydroxyvitamin D (25(OH)D) serum levels <25 nmol/L was defined as vitamin D deficiency and <50 nmol/L as vitamin D insufficiency. Vitamin D-sufficient individuals had a 1.4 years lower mean DNAm age acceleration (p < .05, analysis of variance [ANOVA]) and a 0.11 longer rLTL (p < .001, ANOVA) than vitamin D-deficient participants. Likewise, vitamin D-sufficient participants had lower DNAm age acceleration (β = 1.060, p = .001) and longer rLTL (β = -0.070; p < .001) than vitamin D nonsufficient subjects in covariate-adjusted analysis. Neither DNAm age acceleration nor rLTL were significantly associated with the Fried frailty score or the functional assessments. Only the clock drawing test was associated with DNAm age acceleration (subgroup of older men: β = 1.898, p = .002). Whether the analyzed biomarkers of aging can be used to predict an individual's functional capacity or will be associated with frailty in the advanced course of aging, will be clarified by future longitudinal analyses.

Keywords: Biological age; Epigenetic clock; Frailty; Telomere length; Vitamin D.