BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for BMI
BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for BMI
ABSTRACT BackgroundObesity is a heritable complex phenotype which can increase the risk of age-related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various “epigenetic clocks.” Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely relates with mortality. ObjectivesWe aimed to assess the cross-sectional association of BMI with age acceleration in twins to limit confounding by genetics and shared environment. Methods and ResultsParticipants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twins, and DNAm was measured using the Illumina 450k array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p-value = 6.1 × 10?12) per 1-unit BMI increase. Additionally, heavier twins in a BMI-discordant MZ twin pair (ΔBMI > 3 kg/m2) had an epigenetic age 5.2 months older than their lighter co-twin (p-value = 0.0074). We also found a positive association between log(HOMA-IR) and age acceleration, confirmed by a meta-analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p-value = 0.0025) from adjusted models. ConclusionWe identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance.
Raitakari Olli、Ollikainen Miina、Kuitunen Sara、Pietil?inen Kirsi H.、Hurme Mikko、Perola Markus、Lehtim?ki Terho、Kaprio Jaakko、K?h?nen Mika、M?nnist? Satu、Lundgren Sara
Centre for Population Health Research, University of Turku and Turku University Hospital||Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku||Department of Clinical Physiology and Nuclear Medicine, Turku University HospitalInstitute for Molecular Medicine Finland, FIMM, University of HelsinkiInstitute for Molecular Medicine Finland, FIMM, University of HelsinkiObesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki||Obesity Center, Endocrinology, Abdominal Center, Helsinki University Central Hospital and University of HelsinkiDepartment of Microbiology and Immunology, Faculty of Medicine and Health Technology, Tampere UniversityNational Institute for Health and Welfare||Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of HelsinkiDepartment of Clinical Chemistry, Fimlab Laboratories, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere UniversityInstitute for Molecular Medicine Finland, FIMM, University of HelsinkiDepartment of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere UniversityNational Institute for Health and WelfareInstitute for Molecular Medicine Finland, FIMM, University of Helsinki
基础医学生物科学研究方法、生物科学研究技术
BMIobesityepigenetic clockGrimAgeHOMA-IRaging
Raitakari Olli,Ollikainen Miina,Kuitunen Sara,Pietil?inen Kirsi H.,Hurme Mikko,Perola Markus,Lehtim?ki Terho,Kaprio Jaakko,K?h?nen Mika,M?nnist? Satu,Lundgren Sara.BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for BMI[EB/OL].(2025-03-28)[2025-05-02].https://www.medrxiv.org/content/10.1101/2021.03.11.21253271.点此复制
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