Tuesday, May 13, 2025
5/13/2025
Lifecourse determinants and outcomes of epigenetic age acceleration across two generations - PROJECT SUMMARY/ABSTRACT This study will evaluate the utility of epigenetic age as a new biological marker of aging in a large study that has followed mothers and their offspring for more than 35 years. Aging is a result not only of adult lifestyle, but also of the conditions under which we grow and develop many decades prior. This makes it challenging to study the causes of aging in humans. The recently described “epigenetic clock” records a cumulative index of past experiences while also predicting future mortality, and thus holds promise to allow new approaches to the study of healthy aging and its causes. Epigenetic age is calculated from chemical changes in chromosomes (DNA methylation) that accumulate with high predictability as individuals age. When an individual has an epigenetic age that is advanced relative to their chronological age, they are at increased mortality risk independent of conventional risk factors. This study will measure epigenetic age among participants in the Cebu Longitudinal Health and Nutrition Survey, which has followed several thousand women and their children since 1983. The study is located in Metropolitan Cebu, in the Philippines, which has experienced recent improvements in life expectancy and a corresponding increase in the societal burden of chronic degenerative disease and late life functional decline. The detailed, longitudinal data from this study will be used to address three aims: 1) understand the role of early life development, such as birth size, patterns of growth and weight gain in infancy and childhood, and early life infectious diseases, as predictors of epigenetic age measured in banked DNA samples collected in 2005, when these individuals were young adults (20-22 y); 2) obtain a second DNA sample 15 years later (in 2019-20) and use these new data to study the causes of the rate of change in each individuals' epigenetic age during adulthood; Finally, the study will measure epigenetic age in DNA samples collected in 2005 from these individuals' mothers, which will 3) clarify the domains of functional decline and late life disease, including mortality, that are predicted by epigenetic age. This study is innovative because it uses detailed, longitudinal data collected across two generations to understand the causes and consequences of epigenetic age across the full lifecycle, from birth to old age. The original birth cohort will allow modeling of the developmental factors that influence epigenetic age in early adulthood, while repeat adult epigenetic age measures obtained 15 years apart will clarify which modifiable lifestyle factors predict the pace of biological aging in adulthood. Incorporating the mothers' generation will clarify this biomarker's ability to predict specific pathways of functional decline recently measured in these women, including cognition, memory, and physical ability, along with chronic disease (atherosclerosis) and mortality. This study will thus provide a detailed evaluation of the utility of this promising new biological marker of aging, while also illuminating strategies to promote healthy aging in a population experiencing a rapid increase in the elderly population.
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