Biology subjects

Sabhlok, A.

Publications and source records attributed to Sabhlok, A..

4 recordsLinked to original sources

bioRxiv2023

Stability of DNA-Methylation Profiles of Biological Aging in Children and Adolescents

Background and ObjectivesMethylation profile scores (MPSs) index biological aging and aging-related disease in adults and are cross-sectionally associated with social determinants of health in childhood. MPSs thus provide an opportunity to trace how aging-related biology responds to environmental changes in early life. Information regarding the stability of MPSs in early life is currently lacking. MethodWe use longitudinal data from children and adolescents ages 8-18 (N = 428, M age = 12.15 years) from the Texas Twin Project. Participants contributed two waves of salivary DNA-methylation data (mean lag = 3.94 years), which were used to construct four MPSs reflecting multi-system physiological decline and mortality risk (PhenoAgeAccel and GrimAgeAccel), pace of biological aging (DunedinPACE), and cognitive function (Epigenetic-g). Furthermore, we exploit variation among participants in whether they were exposed to the COVID-19 pandemic during the course of study participation, in order to test how a historical period characterized by environmental disruption might affect childrens aging-related MPSs. ResultsAll MPSs showed moderate longitudinal stability (test-retest rs = 0.42, 0.44, 0.46, 0.51 for PhenoAgeAccel, GrimAgeAccel, and Epigenetic-g, and DunedinPACE, respectively). No differences in the stability of MPSs were apparent between those whose second assessment took place after the onset of the COVID-19 pandemic vs. those for whom both assessments took place prior to the pandemic. ConclusionsAging-related DNA-methylation patterns are less stable in childhood than has been previously observed in adulthood. Further developmental research on the methylome is necessary to understand which environmental perturbations in childhood impact trajectories of biological aging and when children are most sensitive to those impacts. Article SummaryMethylation profiles of biological aging are less stable in childhood than has been previously observed in adulthood. Whats Known on This SubjectMethylation profile scores (MPSs) index biological aging in adults and are cross-sectionally associated with social determinants of health in childhood. Aging-related MPSs in adulthood show very high test-retest stability but data on longitudinal stability of MPSs in childhood is sparse. What This Study AddsChildrens methylation profiles of biological aging are moderately stable across an approximately four-year period. Methylation profiles are less stable in childhood than in adulthood, suggesting that aging-related biology in childhood might be more responsive to environmental changes than in adulthood.

developmental biology↗

bioRxiv2021

Socially stratified epigenetic profiles are associated with cognitive functioning in children and adolescents

Childrens cognitive functioning and educational performance are socially stratified. Social inequality, including classism and racism, may operate partly via epigenetic mechanisms that modulate neurocognitive development. Following preregistered analyses of data from 1,183 8-to 19-year-olds from the Texas Twin Project, we examined whether salivary DNA-methylation measures of inflammation (DNAm-CRP), cognitive functioning (Epigenetic-g), and pace of biological aging (DunedinPoAm) are socially stratified and associated with performance on tests of cognitive functions. We find that children growing up in more disadvantaged families and neighborhoods and children from marginalized racial/ethnic groups exhibit DNA-methylation profiles associated with higher chronic inflammation, lower cognitive functioning, and faster pace of biological aging. These salivary DNA-methylation profiles were associated with processing speed, general executive function, perceptual reasoning, verbal comprehension, reading, and math. Given that the DNA-methylation measures we examined were originally developed in adults, our results suggest that social inequalities may produce in children molecular signatures that, when observed in adults, are associated with chronic inflammation, advanced aging, and reduced cognitive function. Salivary DNA-methylation profiles might be useful as a surrogate endpoint in assessing the effectiveness of psychological and economic interventions that aim to reduce negative effects of childhood social inequality on lifespan development. Significance StatementChildrens cognitive functioning differs by dimensions of social inequality, such as class and race. Epigenetic mechanisms that regulate gene expression might be critically involved in the biological embedding of environmental privilege and adversity. We find that children growing up in more disadvantaged families and neighborhoods and from marginalized racial/ethnic groups exhibit higher chronic inflammation, lower cognitive functioning, and a faster pace of biological aging, as indicated by novel salivary DNA-methylation measures. These DNA-methylation measures of higher inflammation, lower cognitive functioning, and a faster pace of biological aging were, in turn, associated with performance on multiple cognitive tests. DNA-methylation measures might be useful as a surrogate endpoint in evaluation of programs to address the childhood social determinants of lifelong cognitive disparities.

genetics↗

bioRxiv2019

Changing environments reveal innovative genetic variation in children's cortisol responses

Genetic associations with biopsychosocial phenotypes are often interpreted as evidence that the genome codes for fixed end-states. Instead, a given genotype might regulate a dynamic range of phenotypes in response to environmental change. We collected hair cortisol (n = 1,104), salivary cortisol in reaction to an in-laboratory stressor (n = 537), and diurnal salivary cortisol (n = 488) from twins aged 8-15 years in the Texas Twin Project. Baseline genetic variation in both salivary and hair cortisol was not simply magnified after stressor exposure or after waking. Rather, novel genetic influences on cortisol arose over time. Thus, environmental change can reveal genetic variation that would not otherwise be observed in static cortisol levels. These findings are in line with the notion that the genome regulates individuals reactions to the environment that differ across environments.

genetics↗

bioRxiv2019

Weak and uneven associations of home, neighborhood and school environments with stress hormone output across multiple time scales.

The progression of lifelong trajectories of socioeconomic inequalities in health and mortality begins in childhood. Dysregulation in cortisol, a stress hormone that is the primary output of the hypothalamus-pituitary-adrenal (HPA) axis, has been hypothesized to be a mechanism for how early environmental adversity compromises health. However, despite the popularity of cortisol as a biomarker for stress and adversity, little is known about whether cortisol output differs in children being raised in socioeconomically disadvantaged environments. Here, we show that there are few differences between advantaged and disadvantaged children in their cortisol output. In 8- to 14-year-old children from the population-based Texas Twin Project, we measured cortisol output at three different time-scales: (1) diurnal fluctuation in salivary cortisol (n = 400), (2) salivary cortisol reactivity and recovery after exposure to the Trier Social Stress Test (n = 444), and (3) and cortisol concentration in hair (n = 1,210). These measures converged on two moderately correlated, yet distinguishable, dimensions of HPA function. We then tested differences in cortisol output across nine aspects of social disadvantage at the home (e.g., family socioeconomic status), school (e.g., average levels of academic achievement), and neighborhood (e.g., concentrated poverty). Children living in neighborhoods with higher concentrated poverty had higher diurnal cortisol output, as measured in saliva; otherwise, child cortisol output was unrelated to any other aspect of social disadvantage. Overall, we find limited support for alteration in HPA axis functioning as a general mechanism for the health consequences of socioeconomic inequality in childhood.

physiology↗