DNA methylation age acceleration is associated with risk of diabetes complications

Abstract

Background Patients with Type 2 diabetes mellitus (T2D) are at risk for micro- and macrovascular complications. Implementable risk scores are needed to improve targeted prevention for patients that are particularly susceptible to complications. The epigenetic clock estimates an individual’s biological age using DNA methylation profiles. Methods In this study, we examined older adults of the Berlin Aging Study II that were reexamined on average 7.4 years after baseline assessment as part of the GendAge study. DNA methylation age (DNAmA) and its deviation from chronological age DNAmA acceleration (DNAmAA) were calculated with the 7-CpG clock (available at both timepoints, n = 1,071), Horvath’s clock, Hannum’s clock, PhenoAge and GrimAge (available at follow-up only, n = 1,067). T2D associated complications were assessed with the Diabetes Complications Severity Index (DCSI). Results We report on a statistically significant association between oral glucose tolerance test results and Hannum and PhenoAge DNAmAA. PhenoAge was also associated with fasting glucose. In contrast, we found no cross-sectional association after covariate adjustment between DNAmAA and a diagnosis of T2D. However, longitudinal analyses showed that every additional year of 7-CpG DNAmAA at baseline increased the odds for developing one or more additional complications or worsening of an already existing complication during the follow-up period by 11% in male participants with T2D. This association persisted after covariate adjustment (OR = 1.11, p = 0.045, n = 56). Conclusion Although our results remain to be independently validated, this study shows promising evidence of utility of the 7-CpG clock in identifying patients with diabetes who are at high risk for developing complications.

The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus

“…Interestingly, HbA1c levels are associated with other molecular aging markers. HbA1c levels are independently and inversely correlated with telomere length in peripheral blood, genome-wide methylation, and DNA methylation markers of youth 58 , 61 , 76 . Previously, our results showed the roles of the youth-DNA-gap in genomic stability and senescence prevention, and lower numbers of youth-DNA-gaps indicates progressive DNA aging 33 .…”

Low Blood Levels of Selenium, Selenoprotein P and GPx3 are Associated with Accelerated Biological Aging: Results from the Berlin Aging Study II (BASE-II)

“…All other clocks were derived from DNAm data measured by the "Infinium MethylationEPIC" array (Illumina, Inc., USA), data of which was available for n=1,030 participants. Additional information on laboratory procedures and data processing can be found in reference (29). The DunedinPACE clock was calculated based using the methods described in the original publication (24).…”

There are multiple clocks that time us: Cross-sectional and longitudinal associations among 14 alternative indicators of age and aging

“…These indicators are derived from blood assays (epigenetic clocks, pace of aging and telomere length both estimated from epigenetic data (Dunedin PACE and, DNAmTL), laboratory parameters based BioAge), MRI brain scans (brain age), other-ratings (skin age), and self-reports (subjective age, subjective life expectancy, and future health horizon). Some of these biomarkers (epigenetic clocks, telomere length) have already been linked to geriatric, functional and cognitive assessments and frailty 25 , psychological stress 29 , as well as diabetes mellitus (DM) and DM-associated complications 30 in the Berlin Aging Study II (BASE-II). Here, we go several steps further by conducting a comprehensive analysis of available biomarkers in BASE-II to examine how these are interrelated with one another.…”