Epigenetic aging in patients diagnosed with coronary artery disease: results of the LipidCardio study.

INTRODUCTION: People age biologically at different rates. Epigenetic clock-derived DNA methylation age acceleration (DNAmAA) is among the most promising markers proposed to assess the interindividual differences in biological age. Further research is needed to evaluate the characteristics of the different epigenetic clock biomarkers available with respect to the health domains they reflect best. METHODS: In this study, we have analyzed 779 participants of the LipidCardio study (mean chronological age 69.9 ± 11.0 years, 30.6% women) who underwent diagnostic angiography at the Charité University Hospital in Berlin, Germany. DNA methylation age (DNAm age) was measured by methylation-sensitive single nucleotide primer extension (MS-SNuPE) and calculated with the 7-CpG clock. We compared the biological age as assessed as DNAmAA of participants with an angiographically confirmed coronary artery disease (CAD, n = 554) with participants with lumen reduction of 50% or less (n = 90) and patients with a normal angiogram (n = 135). RESULTS: Participants with a confirmed CAD had on average a 2.5-year higher DNAmAA than patients with a normal angiogram. This association did not persist after adjustment for sex in a logistic regression analysis. High-density lipoprotein, low-density lipoprotein, triglycerides, lipoprotein (a), estimated glomerular filtration rate, physical activity, BMI, alcohol consumption, and smoking were not associated with DNAmAA. CONCLUSION: The association between higher DNAmAA and angiographically confirmed CAD seems to be mainly driven by sex.

Cardiovascular health is associated with the epigenetic clock in the Berlin Aging Study II (BASE-II).

The epigenetic clock parameter DNAm age acceleration is a promising biomarker of aging. We have recently described an epigenetic clock based on only seven cytosine-phosphate-guanine sites, which is highly associated with chronological age. The aim of this study was to examine this epigenetic clock with respect to its relationship with cardiovascular health (CVH) in older adults. We used data from the Berlin Aging Study II (BASE-II; 1,671 participants; 68.8 ± 3.7 years old). CVH was operationalized using two different CVH scores, the Framingham Risk Score (FRS), and the Life's simple 7 (LS7). To adjust for potential confounding, e.g. by sex, we performed regression analyses. The LS7 score was higher, i.e. more favorable, in woman than in men (8.8 ± 2 vs. 8.2 ± 2, p < 0.001). DNAm age acceleration was associated with the FRS (ß = 0.122, p = 0.028) and with the LS7 (ß = -0.804, p = 0.032). In more detail, physical activity (ß = -0.461, p = 0.05), HDL-cholesterol (ß = 0.343, p = 0.03) and total cholesterol (ß = -0.364, p = 0.002) were associated with epigenetic age acceleration. We present evidence suggesting that better CVH is associated with decelerated biological aging measured by the epigenetic clock.

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.

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 (ß = 1.060, p = .001) and longer rLTL (ß = -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: ß = 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.