Obesity and accelerated epigenetic aging in a high-risk cohort of children

Abstract

New insights into mechanisms linking obesity to poor health outcomes suggest a role for cellular aging pathways, casting obesity as a disease of accelerated biological aging. Although obesity has been linked to accelerated epigenetic aging in middle-aged adults, the impact during childhood remains unclear. We tested the association between body mass index (BMI) and accelerated epigenetic aging in a cohort of high-risk children. Participants were children (N = 273, aged 8 to 14 years, 82% investigated for maltreatment) recruited to the Child Health Study, an ongoing prospective study of youth investigated for maltreatment and a comparison youth. BMI was measured as a continuous variable. Accelerated epigenetic aging of blood leukocytes was defined as the age-adjusted residuals of several established epigenetic aging clocks (Horvath, Hannum, GrimAge, PhenoAge) along with a newer algorithm, the DunedinPoAm, developed to quantify the pace-of-aging. Hypotheses were tested with generalized linear models. Higher age-and sex- adjusted z-scored BMI was significantly correlated with household income, blood cell counts, and three of the accelerated epigenetic aging measures: GrimAge (r = 0.31, P < .0001), PhenoAge (r = 0.24, P < .0001), and DunedinPoAm (r = 0.38, P < .0001). In fully adjusted models, GrimAge (β = 0.07; P = .0009) and DunedinPoAm (β = 0.0017; P < .0001) remained significantly associated with higher age- and sex-adjusted z-scored BMI. Maltreatment-status was not associated with accelerated epigenetic aging. In a high-risk cohort of children, higher BMI predicted epigenetic aging as assessed by two epigenetic aging clocks. These results suggest the association between obesity and accelerated epigenetic aging begins in early life, with implications for future morbidity and mortality risk.

Pace of aging, family environment and cognitive skills in children and adolescents

“…Additionally, even if it was trained on individuals aged 26, 32, and 38 years old, PoA has been shown to work well also in children and adolescents. (e.g., Belsky et al, 2020 ; Etzel et al, 2022 ; Raffington et al, 2021a ; 2021b ), providing results that are consistent with established findings in the literature on age acceleration in children.…”

The epigenetic aging, obesity, and lifestyle

“…Epigenetic age acceleration at birth and childhood has been associated with maternal habits, including smoking and alcohol consumption during the prenatal period ( Simpkin et al, 2016 ). The link between epigenetic age acceleration with growth and development in early life remains unclear but the trajectory of the blood DNA methylome aging rate appears largely set before adulthood, remaining remarkably stable thereafter ( Etzel et al, 2022 ). Recently, the association between accelerated epigenetic aging and BMI in children using multiple epigenetic clocks has been demonstrated ( Gentilini et al, 2013 ).…”

Epigenetic age acceleration correlates with BMI in young adults

“…Moreover, Quach et al found associations between BMI and both Hannum and Horvath accelerated epigenetic aging indices in 2,725 postmenopausal women (ages 50–82) from the Women’s Health Initiative, although these results were not replicated among 402 males and females from the Italian InCHIANTI cohort (ages 30–100) [ 18 ]. Finally, a recent study of 273 maltreated children (ages 8–14) suggests that the association between BMI and epigenetic aging may emerge as early as in childhood [ 19 ]. Despite these few studies with younger groups, the majority of research on obesity and epigenetic aging has focused on middle-aged and older adults.…”