Significant gaps exist in our understanding of normal aging processes, the impact of these processes on health trajectories, and the influence of exposures as individual’s age. These gaps must be addressed to devise effective therapies that increase health-span. It is well-established that the earliest exposures affecting health- span occur in utero during fetal development. One common challenge, maternal over nutrition (MON) during gestation is an adverse exposure that disproportionally affects individuals from disadvantaged communities. The long-term impacts of MON are important in public health, but difficult to determine in humans due to extensive confounding by multiple environmental and social factors. The baboon is a nonhuman primate (NHP) species highly similar to humans in genetics, physiology, and metabolism, and naturally develops age- associated diseases. We have been studying baboons longitudinally to examine the impact of a Western diet on age-associated diseases, and dissect the impact of MON on health-span. In Cycle 1 of this U19 we hypothesized that MON leads to accelerated aging, but with similar trajectories to normal aging. Our studies have shown that in utero MON developmentally programs (DP) molecular, cellular, and functional processes, leading to fundamentally different aging processes and trajectories compared to healthy aging animals. An understanding of underlying molecular mechanisms that differ due to exposures is essential for development of therapies that target appropriate systems. In Cycle 2 of the U19 we propose to integrate discoveries from molecules with whole animal measures to better understand established and novel hallmarks of aging. For these planned studies in Cycle 2 to be feasible, it is essential that we maintain the unique cohort of MON animals and their age-matched controls. The requested bridge funds will cover animal per diems of the cohort to guarantee that these animals are not assigned to other studies at the Southwest National Primate Research Center during the NCE of our U19 program.

Significant gaps exist in our understanding of how a suboptimal in utero environment impacts aging processes and trajectories. We have developed a unique cohort of baboons exposed in utero to maternal overnutrition in order to determine how this suboptimal environment during fetal developmental impacts aging in adult offspring. The requested bridge funds will cover animal per diems of the cohort that are central to our U19 program, which is essential for the U19 renewal resubmission, with maintained support essential to guarantee that these animals are not assigned to other studies at the Southwest National Primate Research Center.