Relationship between five Epigenetic Clocks, Telomere Length and Functional Capacity assessed in Older Adults: Cross-sectional and Longitudinal Analyses

Abstract

DNA methylation age acceleration (DNAmAA, derived from an epigenetic clock) and relative leukocyte telomere length (rLTL) are widely accepted biomarkers of aging. Nevertheless, it is still unclear which aspects of aging they represent best. Here we evaluated longitudinal associations between baseline rLTL and DNAmAA (estimated with 7-CpG clock) and functional assessments covering different domains of aging. Additionally, we made use of cross-sectional data on these assessments and examined their association with DNAmAA estimated by five different DNAm age measures. Two-wave longitudinal data was available for 1,083 participants of the Berlin Aging Study II (BASE-II) who were re-examined on average 7.4 years after baseline as part of the GendAge study. Functional outcomes were assessed with Frieds frailty score, Tinetti mobility test, falls in the past 12 months (yes/no), Finger-floor distance, Mini Mental State Examination (MMSE), Center for Epidemiologic Studies Depression Scale (CES-D), Activities of Daily Living (ADL), Instrumented ADL (IADL) and Mini Nutritional Assessment (MNA). Overall, we found no evidence for an association between the molecular biomarkers measured at baseline, rLTL and DNAmAA (7-CpG clock), and functional assessments assessed at follow-up. Similarly, a cross-sectional analyses of follow-up data did also not show evidence for associations of the various DNAmAA measures (7-CpG clock, Horvaths clock, Hannums clock PhenoAge, and GrimAge) with functional assessments. In conclusion, neither rLTL nor 7-CpG DNAmAA were able to predict impairment in the analyzed assessments over a [~]7 year time-course. Similarly, DNAmAA as estimated by five epigenetic clocks was not a good cross-sectional marker of health deterioration either.