DNA-methylation profiles of child development in adult aging

Objectives: 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 children. This research indicates that biological aging is affected by childhood environments and shows overlap with developmental processes. 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 probed if MPSs that reflect childhood development are associated with physical and psychological aging later in life.
Study design: Here we examine whether MPSs quantifying childhood socioeconomic contexts and developmental processes – computed in adults– are related to their adult health. We will use published algorithms developed in child methylation samples and apply them to methylation data from the HRS. We focus on MPSs of socioeconomic contexts, age, gestational age, birthweight, and pubertal timing measured in children and adolescents. We will test whether these MPSs computed in adults are related to their health, mortality, retrospective reports of childhood poverty, as well as their MPSs of biological aging.
Analysis plan: In preregistered multiple regressions analyses, we will test for associations of MPSs of childhood exposures and development with physical health (BMI, menopause, functional limitations, multimorbidity, mortality), mental health (cognitive impairment, depression), childhood poverty index, and biological aging (PhenoAge, GrimAge and DunedinPACE). Sex and cell composition will be included as covariate controls, and we will test whether associations hold after accounting for substance use, racial identity, and adult SES.

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. Research shows that biological aging is affected by childhood environments and shows overlap with “developmental processes” (e.g., puberty, cognition). Because the MPSs were computed using algorithms developed in adults, these studies indicate a molecular link between childhood environments, development, and adult biological aging. Researchers have not yet probed if MPSs that reflect exposures in childhood or child development are associated with physical and psychological aging later in life. Here we examine whether MPSs quantifying childhood socioeconomic contexts and child developmental processes – computed in adults from the Health and Retirement study – are related to their adult physical and psychological health. By applying MPSs developed in child samples to older adults, we can potentially unravel how early-life factors contribute to later-life health and aging.