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

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

doi:10.1111/joim.13528

Cited by 32 publications

(20 citation statements)

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“…The results derived from the replication of the individual-level analyses in a large Finnish cohort study were apparently similar to those derived from the primary analyses, providing additional evidence that also high blood pressure is associated with accelerated aging. These findings are in line with previous research related to the association between MetS and epigenetic aging [ 8 , 9 , 15 , 17 – 19 , 38 ].…”

Section: Discussionsupporting

confidence: 93%

Metabolic syndrome and epigenetic aging: a twin study

Föhr,

Hendrix,

Kankaanpää

et al. 2024

Int J Obes

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Background Metabolic syndrome (MetS) is associated with premature aging, but whether this association is driven by genetic or lifestyle factors remains unclear. Methods Two independent discovery cohorts, consisting of twins and unrelated individuals, were examined (N = 268, aged 23–69 years). The findings were replicated in two cohorts from the same base population. One consisted of unrelated individuals (N = 1 564), and the other of twins (N = 293). Participants’ epigenetic age, estimated using blood DNA methylation data, was determined using the epigenetic clocks GrimAge and DunedinPACE. The individual-level linear regression models for investigating the associations of MetS and its components with epigenetic aging were followed by within-twin-pair analyses using fixed-effects regression models to account for genetic factors. Results In individual-level analyses, GrimAge age acceleration was higher among participants with MetS (N = 56) compared to participants without MetS (N = 212) (mean 2.078 [95% CI = 0.996,3.160] years vs. −0.549 [−1.053,−0.045] years, between-group p = 3.5E-5). Likewise, the DunedinPACE estimate was higher among the participants with MetS compared to the participants without MetS (1.032 [1.002,1.063] years/calendar year vs. 0.911 [0.896,0.927] years/calendar year, p = 4.8E-11). An adverse profile in terms of specific MetS components was associated with accelerated aging. However, adjustments for lifestyle attenuated these associations; nevertheless, for DunedinPACE, they remained statistically significant. The within-twin-pair analyses suggested that genetics explains these associations fully for GrimAge and partly for DunedinPACE. The replication analyses provided additional evidence that the association between MetS components and accelerated aging is independent of the lifestyle factors considered in this study, however, suggesting that genetics is a significant confounder in this association. Conclusions The results of this study suggests that MetS is associated with accelerated epigenetic aging, independent of physical activity, smoking or alcohol consumption, and that the association may be explained by genetics.

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Section: Discussionsupporting

confidence: 93%

Metabolic syndrome and epigenetic aging: a twin study

Föhr,

Hendrix,

Kankaanpää

et al. 2024

Int J Obes

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“…In the fifth step, a class of participants with high BMI was extracted. Previous studies have shown the role of being overweight or obese in biological aging ( Lundgren et al, 2022 ). After including the sixth class, the information criteria still showed considerable improvement, but the AvePPs for several classes were below 0.8.…”

Section: Resultsmentioning

confidence: 99%

The role of adolescent lifestyle habits in biological aging: A prospective twin study

Kankaanpää

Tolvanen

Heikkinen

et al. 2022

eLife

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Background:Adolescence is a stage of fast growth and development. Exposures during puberty can have long-term effects on health in later life. This study aims to investigate the role of adolescent lifestyle in biological aging.Methods:The study participants originated from the longitudinal FinnTwin12 study (n = 5114). Adolescent lifestyle-related factors, including body mass index (BMI), leisure-time physical activity, smoking, and alcohol use, were based on self-reports and measured at ages 12, 14, and 17 years. For a subsample, blood-based DNA methylation (DNAm) was used to assess biological aging with six epigenetic aging measures in young adulthood (21–25 years, n = 824). A latent class analysis was conducted to identify patterns of lifestyle behaviors in adolescence, and differences between the subgroups in later biological aging were studied. Genetic and environmental influences on biological aging shared with lifestyle behavior patterns were estimated using quantitative genetic modeling.Results:We identified five subgroups of participants with different adolescent lifestyle behavior patterns. When DNAm GrimAge, DunedinPoAm, and DunedinPACE estimators were used, the class with the unhealthiest lifestyle and the class of participants with high BMI were biologically older than the classes with healthier lifestyle habits. The differences in lifestyle-related factors were maintained into young adulthood. Most of the variation in biological aging shared with adolescent lifestyle was explained by common genetic factors.Conclusions:These findings suggest that an unhealthy lifestyle during pubertal years is associated with accelerated biological aging in young adulthood. Genetic pleiotropy may largely explain the observed associations.Funding:This work was supported by the Academy of Finland (213506, 265240, 263278, 312073 to J.K., 297908 to M.O. and 341750, 346509 to E.S.), EC FP5 GenomEUtwin (J.K.), National Institutes of Health/National Heart, Lung, and Blood Institute (grant HL104125), EC MC ITN Project EPITRAIN (J.K. and M.O.), the University of Helsinki Research Funds (M.O.), Sigrid Juselius Foundation (J.K. and M.O.), Yrjö Jahnsson Foundation (6868), Juho Vainio Foundation (E.S.) and Päivikki and Sakari Sohlberg foundation (E.S.).

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“…A connection exists between Body Mass Index (BMI) and aging. Lundgren et al ( 53 ) found that higher BMIs correlate positively with accelerated epigenetic aging. Santos et al ( 54 ) discussed the molecular mechanisms connecting obesity with aging, emphasizing the similarities in metabolic dysfunction and the potential for obesity to speed up aging.…”

Section: Discussionmentioning

confidence: 99%

Better Life’s Essential 8 contributes to slowing the biological aging process: a cross-sectional study based on NHANES 2007–2010 data

Wu,

Qu,

Huang

et al. 2024

Front. Public Health

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ObjectiveTo investigate the relationship between Life’s Essential 8 (LE8) and Phenotypic Age Acceleration (PhenoAgeAccel) in United States adults and to explore the impact of LE8 on phenotypic biological aging, thereby providing references for public health policies and health education.MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2010, this cross-sectional study analyzed 7,339 adults aged 20 and above. Comprehensive assessments of LE8, PhenoAgeAccel, and research covariates were achieved through the integration of Demographics Data, Dietary Data, Laboratory Data, and Questionnaire Data derived from NHANES. Weighted generalized linear regression models and restricted cubic spline plots were employed to analyze the linear and non-linear associations between LE8 and PhenoAgeAccel, along with gender subgroup analysis and interaction effect testing.Results(1) Dividing the 2007–2010 NHANES cohort into quartiles based on LE8 unveiled significant disparities in age, gender, race, body mass index, education level, marital status, poverty-income ratio, smoking and drinking statuses, diabetes, hypertension, hyperlipidemia, phenotypic age, PhenoAgeAccel, and various biological markers (p < 0.05). Mean cell volume demonstrated no intergroup differences (p > 0.05). (2) The generalized linear regression weighted models revealed a more pronounced negative correlation between higher quartiles of LE8 (Q2, Q3, and Q4) and PhenoAgeAccel compared to the lowest LE8 quartile in both crude and fully adjusted models (p < 0.05). This trend was statistically significant (p < 0.001) in the full adjustment model. Gender subgroup analysis within the fully adjusted models exhibited a significant negative relationship between LE8 and PhenoAgeAccel in both male and female participants, with trend tests demonstrating significant results (p < 0.001 for males and p = 0.001 for females). (3) Restricted cubic spline (RCS) plots elucidated no significant non-linear trends between LE8 and PhenoAgeAccel overall and in gender subgroups (p for non-linear > 0.05). (4) Interaction effect tests denoted no interaction effects between the studied stratified variables such as age, gender, race, education level, and marital status on the relationship between LE8 and PhenoAgeAccel (p for interaction > 0.05). However, body mass index and diabetes manifested interaction effects (p for interaction < 0.05), suggesting that the influence of LE8 on PhenoAgeAccel might vary depending on an individual’s BMI and diabetes status.ConclusionThis study, based on NHANES data from 2007–2010, has revealed a significant negative correlation between LE8 and PhenoAgeAccel, emphasizing the importance of maintaining a healthy lifestyle in slowing down the biological aging process. Despite the limitations posed by the study’s design and geographical constraints, these findings provide a scientific basis for the development of public health policies focused on healthy lifestyle practices. Future research should further investigate the causal mechanisms underlying the relationship between LE8 and PhenoAgeAccel and consider cross-cultural comparisons to enhance our understanding of healthy aging.

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

Cited by 32 publications

References 59 publications

Metabolic syndrome and epigenetic aging: a twin study

Metabolic syndrome and epigenetic aging: a twin study

The role of adolescent lifestyle habits in biological aging: A prospective twin study

Better Life’s Essential 8 contributes to slowing the biological aging process: a cross-sectional study based on NHANES 2007–2010 data

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