A life course perspective on the effects of cumulative early adversity on health

总结

Summary The long arm of early life remains one of the most enduring puzzles in human health. To date, two classes of evolutionary models have been proposed to address this puzzle. Developmental constraints models propose that early adversity leads to tradeoffs with somatic investment during development, with long-term, negative consequences for health. Predictive models propose that organisms use early adversity to predict future circumstances, making developmental adjustments that optimize Darwinian fitness in adulthood. The relative merits of these models have been difficult to establish, especially in humans and other long-lived species. Resolving this debate is necessary to understand the developmental origins of health and disease and to identify efficient methods to mitigate early life effects. The primary objective of this proposal is to test predictive and constraints frameworks by characterizing diverse developmental, health, fitness, and aging-related outcomes arising from variation in early life adversity. It accomplishes this objective in a non-human primate model that is offers an excellent comparative system to understand the evolutionary pressures faced by early humans. This system also offers real-time data on several forms of early adversity and multiple longitudinal developmental, behavioral, and health outcomes in response to early adversity. This project tests the central hypotheses that: (i) responses to early adversity are dominated by developmental constraints, leading to restricted somatic investment, delayed reproductive schedules, lower fertility, and accelerated aging; but (ii) these responses can be mitigated by positive social conditions in adulthood. Aim 1 distinguishes constraints and predictive responses in the juvenile period. Aim 2 contributes a strong test of predictive and constraints models by testing adult responses in both low and high quality environments. Aim 3 tests the potential for social support to mitigate the negative effects of early adversity, offering avenues to ameliorate these effects in adulthood. By spanning multiple sources of adversity and multiple aspects of somatic and reproductive health, this project will contribute the most comprehensive test to distinguish predictive and constraints frameworks in any species to date. Establishing which model dominates is critical to predict how environments in adulthood will interact with early adversity to shape adult health, and how to best mitigate responses to early adversity. Specifically, constraints models predict that mitigation should focus on early life. In contrast predictive models posit that optimal mitigation strategies will differ depending on which sources of early adversity individuals experienced. By disentangling responses to adversity, this project will improve basic understanding of the developmental origins of health and disease and lend key insight into how different sources of adversity interact with good and bad conditions in adulthood to shape adult health and rates of aging.