Using Epigenetic Clocks to Characterize Biological Aging in Studies of Children and Childhood Exposures: a Systematic Review

Musci, Rashelle J.; Raghunathan, Radhika S.; Johnson, Sara B.; Klein, Lauren R.; Ladd‐Acosta, Christine; Ansah, Rosemary; Hassoun, Roua; Voegtline, Kristin

doi:10.1007/s11121-023-01576-4

Cited by 9 publications

(2 citation statements)

References 98 publications

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“…In the Texas Twin Project, we found children from underserved families to have MPSs indicating advanced biological age, a faster pace of aging, higher chronic inflammation, higher BMI, and lower cognitive health 26,34,46 . Some of these findings have been replicated in buccal samples from the German SOEP-G sample 27 , as well as the Future Families and Child Well-Being Study, where we found socioeconomic contexts at birth relative to concurrent socioeconomic contexts in childhood and adolescence to be most strongly associated with MPS of BMI in childhood and adolescence ( 26,47 ; for review see also 48 ). Racial and ethnic disparities in children's biological aging were reduced, but remained visible, after statistically accounting for perinatal and postnatal covariates, including the substantially higher risk of socioeconomic disadvantage in racially marginalized communities.…”

Section: Quantifying Biological Aging Early In the Life Spansupporting

confidence: 57%

Utilizing epigenetics to study the shared nature of development and biological aging across the lifespan

Raffington

2024

npj Sci. Learn.

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Recently, biological aging has been quantified in DNA-methylation samples of older adults and applied as so-called “methylation profile scores” (MPSs) in separate target samples, including samples of children. This nascent research indicates that (1) biological aging can be quantified early in the life course, decades before the onset of aging-related disease, (2) is affected by common environmental predictors of childhood development, and (3) shows overlap with “developmental processes” (e.g., puberty). Because the MPSs were computed using algorithms developed in adults, these studies indicate a molecular link between childhood environments, development, and adult biological aging. Yet, if MPSs can be used to connect development and aging, previous research has only traveled one way, deriving MPSs developed in adults and applying them to samples of children. Researchers have not yet quantified epigenetic measures that reflect the pace of child development, and tested whether resulting MPSs are associated with physical and psychological aging. In this perspective I posit that combining measures of biological aging with new quantifications of child development has the power to address fundamental questions about life span: How are development and experience in childhood related to biological aging in adulthood? And what is aging?

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Section: Quantifying Biological Aging Early In the Life Spansupporting

confidence: 57%

Utilizing epigenetics to study the shared nature of development and biological aging across the lifespan

Raffington

2024

npj Sci. Learn.

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“…The clock variation we observe in this cohort could reflect both causal patterns. Prior studies establish that the epigenetic clocks are variable in young people who do not yet have disease and that they are sensitive to exposures known to cause disease well in advance of disease onset ( 38 , 39 ). In our own analysis, we find that famine associations with accelerated aging, particularly the DunedinPACE clock, are independent of prevalent morbidity associated with famine exposure.…”

Section: Discussionmentioning

confidence: 99%

Accelerated biological aging six decades after prenatal famine exposure

Cheng,

Conley,

Kuipers

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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To test the hypothesis that early-life adversity accelerates the pace of biological aging, we analyzed data from the Dutch Hunger Winter Families Study (DHWFS, N = 951). DHWFS is a natural-experiment birth-cohort study of survivors of in-utero exposure to famine conditions caused by the German occupation of the Western Netherlands in Winter 1944 to 1945, matched controls, and their siblings. We conducted DNA methylation analysis of blood samples collected when the survivors were aged 58 to quantify biological aging using the DunedinPACE, GrimAge, and PhenoAge epigenetic clocks. Famine survivors had faster DunedinPACE, as compared with controls. This effect was strongest among women. Results were similar for GrimAge, although effect-sizes were smaller. We observed no differences in PhenoAge between survivors and controls. Famine effects were not accounted for by blood-cell composition and were similar for individuals exposed early and later in gestation. Findings suggest in-utero undernutrition may accelerate biological aging in later life.

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Longitudinal Changes in Epigenetic Age Acceleration Across Childhood and Adolescence

Del Toro,

Martz,

Freilich

et al. 2024

JAMA Pediatr

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ImportanceIndividuals exposed to discrimination may exhibit greater epigenetic age acceleration (ie, cellular indicators of premature aging) over time, but few studies have examined longitudinal changes in epigenetic age acceleration, the heterogeneity in these changes for diverse groups of youths, and contextual explanations (ie, discrimination) for differences by ethnicity or race.ObjectiveTo provide a descriptive illustration of changes in epigenetic age acceleration across childhood and adolescence among an ethnically and racially diverse sample of youths.Design, Setting, and ParticipantsThis cohort study leveraged longitudinal data on a large sample of youths from low-income households in 20 large urban US cities who provided repeated assessments of saliva tissue samples at ages 9 and 15 years for DNA methylation analysis. Of 4898 youths from the Future of Families and Child Well-Being study, an ongoing study that oversampled children born to unmarried parents from 1998 to 2000, 2039 were included in the present analysis, as these youths had salivary DNA methylation data assayed and publicly available. Analyses were conducted from March 2023 to June 2024.ExposuresRacialized intrusive encounters with police (eg, stop and frisk and racial slurs).Main Outcomes and MeasuresAnalyses were conducted to examine longitudinal changes in salivary epigenetic age acceleration over time, whether such changes varied across ethnically and racially diverse groups of youths, and whether police intrusion was associated with variation across ethnic and racial groups.ResultsAmong 2039 youths (mean [SD] age at baseline, 9.27 [0.38] years; 1023 [50%] male and 1016 [50%] female; 917 [45%] Black, 430 [21%] Hispanic or Latino, 351 [17%] White, and 341 [17%] other, including multiple races and self-identified other) with salivary epigenetic clocks at 9 and 15 years of age, longitudinal results showed that White youths exhibited less accelerated epigenetic aging over time than did Black and Hispanic or Latino youths and those reporting other or multiple races or ethnicities from ages 9 to 15 years, particularly in the Hannum (B, 1.54; 95% CI, 0.36-2.18), GrimAge (B, 1.31; 95% CI, 0.68-1.97), and DunedinPACE epigenetic clocks (B, 0.27; 95% CI, 0.11-0.44). Across these clocks and the PhenoAge clock, police intrusion was associated with Black youths’ more accelerated epigenetic aging (Hannum: B, 0.11; 95% CI, 0.03-0.23; GrimAge: B, 0.09; 95% CI, 0.03-0.18; PhenoAge: B, 0.08; 95% CI, 0.02-0.18; DunedinPACE: B, 0.01; 95% CI, 0.01-0.03).Conclusions and RelevanceThe transition from childhood to adolescence may represent a sensitive developmental period when racism can have long-term deleterious impacts on healthy human development across the life span. Future research should build on the present study and interrogate which social regularities and policies may be perpetuating discrimination against ethnically and racially minoritized adolescents.

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Using Epigenetic Clocks to Characterize Biological Aging in Studies of Children and Childhood Exposures: a Systematic Review

Cited by 9 publications

References 98 publications

Utilizing epigenetics to study the shared nature of development and biological aging across the lifespan

Utilizing epigenetics to study the shared nature of development and biological aging across the lifespan

Accelerated biological aging six decades after prenatal famine exposure

Longitudinal Changes in Epigenetic Age Acceleration Across Childhood and Adolescence

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