Dataset Information

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

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.

SUBMITTER: Lundgren S

PROVIDER: S-EPMC9540898 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Lundgren Sara S Kuitunen Sara S Pietiläinen Kirsi H KH Hurme Mikko M Kähönen Mika M Männistö Satu S Perola Markus M Lehtimäki Terho T Raitakari Olli O Kaprio Jaakko J Ollikainen Miina M

Journal of internal medicine 20220708 4

<h4>Background</h4>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.<h4>Objectives</h4>We aimed to assess the cross-sectional ass ...[more]

PMID: 35699258

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Project description:Background Subcutaneous adipose tissue (SAT) undergoes major changes in obesity, but little is known about the whole-genome scale patterns of these changes or about their variation between different obesity subgroups. We sought to compare how transcriptomics profiles in SAT differ between monozygotic (MZ) co-twins who are discordant for body mass index (BMI), whether the profiles vary between twin pairs and whether the variation can be linked to clinical characteristics. Methods We analyzed the transcriptomics (Affymetrix U133 Plus 2.0) patterns of SAT in young MZ twin pairs (n =26, intrapair difference in BMI>3 kg/m2, aged 23-36), from 10 birth cohorts of adult Finnish twins. The clinical data included measurements of body composition, insulin resistance, lipids, and adipokines. Results We found 2108 genes differentially expressed (FDR<0.05) in SAT of the BMI-discordant pairs. Pathway analyses of these genes revealed a significant downregulation of mitochondrial oxidative pathways (p<0.05) and upregulation of inflammation pathways (p<0.05). Hierarchical clustering of heavy/lean twin ratios, representing effects of acquired obesity in the transcriptomics data, revealed three sub-groups with different molecular profiles (FDR<0.05). Analyses comparing these sub-groups showed that, in the heavy co-twins, downregulation of the mitochondrial pathways, especially that of branched chain amino acid (BCAA) degradation was more evident in two last clusters while and upregulation of the inflammatory response was most evident in the last, presumably the unhealthiest cluster. High fasting insulin levels and large adipocyte diameter were the predominant clinical characteristic of the heavy co-twins in this cluster (Bonferroni adjusted p<0.05). Conclusions This is the first study in BMI-discordant MZ twin pairs reporting sub-types of obesity based on both SAT gene expression profiles and clinical traits. We conclude that a decrease in mitochondrial BCAA degradation and an increase in inflammation in SAT co-occur and associate with hyperinsulinemia and large adipocyte size in unhealthy obesity.

Dataset Information

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

Background

Objectives

Methods and results

Conclusion

Publications

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

Similar Datasets

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