Epigenome-wide analysis of frailty: Results from two European twin cohorts.

Autor: Mak JKL; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Skovgaard AC; The Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense M, Denmark., Nygaard M; The Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense M, Denmark., Kananen L; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Faculty of Social Sciences (Health Sciences) and Gerontology Research Center (GEREC), University of Tampere, Tampere, Finland., Reynolds CA; Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, USA.; Department of Psychology, University of California, Riverside, California, USA., Wang Y; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden., Kuja-Halkola R; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Karlsson IK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Pedersen NL; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Hägg S; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Soerensen M; The Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense M, Denmark.; Department of Clinical Genetics, Odense University Hospital, Odense C, Denmark., Jylhävä J; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Faculty of Social Sciences (Health Sciences) and Gerontology Research Center (GEREC), University of Tampere, Tampere, Finland.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Jun; Vol. 23 (6), pp. e14135. Date of Electronic Publication: 2024 Feb 27.
DOI: 10.1111/acel.14135
Abstrakt: Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index (FI), and DNA methylation levels were measured in whole blood using Illumina's Infinium HumanMethylation450K and MethylationEPIC arrays. In the meta-analysis consisting of a total of 829 participants, we identified 589 CpG sites that were statistically significantly associated with either the continuous or categorical FI (false discovery rate <0.05). Many of these CpGs have previously been associated with age and age-related diseases. The identified sites were also largely directionally consistent in a longitudinal analysis using mixed-effects models in SATSA, where the participants were followed up to a maximum of 20 years. Moreover, we identified three differentially methylated regions within the MGRN1, MIR596, and TAPBP genes that have been linked to neuronal aging, tumor growth, and immune functions. Furthermore, our meta-analysis results replicated 34 of the 77 previously reported frailty-associated CpGs at p < 0.05. In conclusion, our findings demonstrate robust associations between frailty and DNA methylation levels in 589 novel CpGs, previously unidentified for frailty, and strengthen the role of neuronal/brain pathways in frailty.
(© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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