BMI is positively associated with accelerated epigenetic aging in twin pairs discordant for body mass index

Sara Lundgren, Sara Kuitunen, Kirsi H. Pietiläinen, Mikko Hurme, Mika Kähönen, Satu Männistö, Markus Perola, Terho Lehtimäki, Olli Raitakari, Jaakko Kaprio, Miina Ollikainen

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Background: Obesity is a heritable complex phenotype that 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 correlates with mortality. Objectives: We aimed to assess the cross-sectional association of body mass index (BMI) with age acceleration in twins to limit confounding by genetics and shared environment. Methods and results: Participants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twin pairs, 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 one-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 cotwin (p-value = 0.0074). We also found a positive association between log (homeostatic model assessment of insulin resistance) and age acceleration, confirmed by a meta-analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p-value = 4.1 × 10–25) from adjusted models. Conclusion: We 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.

Original languageEnglish
Number of pages14
JournalJOURNAL OF INTERNAL MEDICINE
Volume292
Issue number4
DOIs
Publication statusPublished - 2022
Publication typeA1 Journal article-refereed

Keywords

  • aging
  • BMI
  • epigenetic clock
  • GrimAge
  • HOMA-IR
  • obesity

Publication forum classification

  • Publication forum level 2

ASJC Scopus subject areas

  • Internal Medicine

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