Doctoral Dissertation Research: Epigenetics of primate longevity

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Humans are long-lived compared with other mammals, including our closest living biological relatives, the chimpanzees. Yet the genetic and physiological bases of our remarkable longevity, as well as the processes underlying human aging, remain poorly understood. This project uses a comparative molecular approach to elucidate the unique human pattern of aging and long life by comparing the genetic regulatory changes that occur with age in chimpanzees with those observed in humans. Specifically, researchers will investigate the chemical alterations to DNA called methylation. Methylation is proving to be an important mechanism, via the adjustment of gene expression levels, in the control of temporal biological processes, including development and potentially aging. Results of this project will allow for the identification of genes that are differently regulated with age in the two species and thereby help identify which physiological mechanisms (for example, DNA damage repair or immune function) play critical roles specifically in human survival to advanced ages. This project has important current relevance because human populations are aging demographically at an unprecedented rate, and the need to manage and treat age-related medical issues is rapidly growing. This project will contribute to the training of graduate and undergraduate students in laboratory and analytical techniques and will relay results related to aging to members of the public through free educational programming.A growing body of recent research demonstrates a strong pattern of change in methylation levels at sites across the genome with age in humans that are so predictable that they can be used to estimate individual chronological age. Moreover, slight deviations among individuals in "methylation age" seem to reflect biological aging: elevated methylation age is associated with mortality risk, increased frailty, decreased grip strength and lung function, diminished cognitive performance, and increased cancer and cardiovascular disease risk. Thus, methylation age represents a valuable new approach for measuring biological aging, identifying factors that influence aging rate, and potentially uncovering the genetic regulatory changes that underlie physiological aging. The current study will generate genome-wide methylomes from 100 chimpanzee DNA samples collected from individuals aged 0 to 59 and identify which sites show changes in methylation levels with age. These data will be compared with existing human datasets to discover differences in the methylome landscape and methylation aging rate between the two species. Thus, this project extends the study of methylation age to a cross-species comparative context to illuminate the evolution of fundamental differences in life history between humans and other primates.