Epigenome‐wide analysis of frailty: Results from two European twin cohorts
Year: 2024
Type: article
Abstract: 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.
Source: Aging Cell
DOI: 10.1111/acel.14135
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,350
Funders: John D. and Catherine T. MacArthur Foundation, Yrjö Jahnssonin Säätiö, Wellcome Trust, Loo och Hans Ostermans Stiftelse för Medicinsk Forskning, European Commission, Forskningsrådet för Arbetsliv och Socialvetenskap, Fondation pour la Recherche Médicale, Juho Vainion Säätiö, Karolinska Institutet, Päivikki ja Sakari Sohlbergin Säätiö, Vetenskapsrådet, Norges Forskningsråd, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Sigrid Juséliuksen Säätiö, Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Tampereen Tuberkuloosisäätiö, National Institutes of Health, National Institute on Aging, Fabrikant Vilhelm Pedersen og Hustrus Legat
Awards: GENETIC AND ENVIRONMENTAL INFLUENCES IN BEHAVIORAL AGING, G1690567459, G181866454, Why do some people become frail as they age while others do not? A life course approach to identifying genetic, epigenetic and environmental risk factors for frailty., G2476663878, Oldest-old Mortality - Demographic Models and Analysis, G335306573, G3394914194, G37339782, G4781335763, G5702163051, Drug repurposing for age-related diseases using Mendelian Randomizations on large individual-level genomic data, Genetic & Environmental Influences-Biobehavioral Aging, G712881263, Epigenetic signatures of inflammation in relation to brain structure and connectivity across the lifecourse, G8479256176, G8499346954, Wuhan Interaction with Stockholm Evidence-based Research (WISER) project on health perspectives in the older population facing the SARS-CoV-2 outbreak, G9000251321
OpenAlex ID: W4392237293