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Epigenome-wide analysis of frailty: Results from two European twin cohorts.
Mak, Jonathan K L; Skovgaard, Asmus Cosmos; Nygaard, Marianne; Kananen, Laura; Reynolds, Chandra A; Wang, Yunzhang; Kuja-Halkola, Ralf; Karlsson, Ida K; Pedersen, Nancy L; Hägg, Sara; Soerensen, Mette; Jylhävä, Juulia.
Affiliation
  • Mak JKL; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Skovgaard AC; Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Nygaard M; The Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense M, Denmark.
  • Kananen L; The Danish Twin Registry and Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense M, Denmark.
  • Reynolds CA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Wang Y; Faculty of Social Sciences (Health Sciences) and Gerontology Research Center (GEREC), University of Tampere, Tampere, Finland.
  • Kuja-Halkola R; Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado, USA.
  • Karlsson IK; Department of Psychology, University of California, Riverside, California, USA.
  • Pedersen NL; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Hägg S; Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
  • Soerensen M; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Jylhävä J; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Aging Cell ; 23(6): e14135, 2024 06.
Article in En | MEDLINE | ID: mdl-38414347
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA Methylation / Frailty / Epigenome Limits: Aged / Aged80 / Female / Humans / Male Language: En Journal: Aging Cell Year: 2024 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: DNA Methylation / Frailty / Epigenome Limits: Aged / Aged80 / Female / Humans / Male Language: En Journal: Aging Cell Year: 2024 Document type: Article Affiliation country: Country of publication: