Effects of age and social adversity on immune status and responsiveness in a non-human primate model of human aging - Project Summary The average human lifespan has almost doubled over the past century, leading to an increase in the prevalence of diseases of aging, such as cardiovascular disease, arthritis, cognitive decline and autoimmune disorders. Aging is associated with a decline in adaptive immune function and an increase in inflammation, which underlie many age-related diseases. These immunological changes are similar to those seen in individuals exposed to social adversity, who may age more rapidly than those unexposed. Yet, it is unclear how social adversity alters immunity across demographic factors - data that are essential to identify how it might increase aging-related diseases. The central objective of this proposal is to identify the specific cell types and molecular markers of the immune system that contribute to the aging process and how social adversity shapes the function of these cells and markers. To test this, I draw on a longitudinal study of free-ranging nonhuman primates – the Cayo Santiago rhesus macaques. These animals present a unique opportunity to examine aging and its social determinants. First, rhesus macaques have a strong phylogenetic proximity to humans and show very similar aging trajectories, making them an exceptional model for human health. Second, rhesus macaques form stable social structures that dictate individuals' access to resources and peers, similar to human populations- making this species an ideal model in which to study the potential effect that social adversity has on accelerating aging. The central hypothesis of this proposal is that social adversity leads to an impaired immune system, recapitulating the effects of aging, which consequently accelerates the biological signatures of aging independently of an individual’s chronological age. To test this hypothesis, I will collect data from the Cayo Santiago rhesus macaque population over two years, totaling a sample size of 200 individuals. Aim 1 of this proposal will measure and explore how both age social adversity and age alter immunity at baseline by measuring different immune cell types – both lymphocytes and monocyte subpopulations- using flow cytometry. Aim 2 of this project will test how age and social adversity alter the immune response to an infection, and if they do so in a similar way. Here, we will create a pro-inflammatory (Th1) and anti-inflammatory (Th2) immune response by isolating and stimulating peripheral blood mononuclear cells (PBMCs) using live pathogens and pathogens molecules. In recent years, it has become clear that the social environment plays a critical role in the development and overall health across different species. By combining physiological data and behavioral observations, the proposed project will generate data that is necessary to understand the role that social adversity may play in inducing aging-related changes in immunity. Ultimately, this project will reveal how the social environment alters the pace of aging, which will inform the targeted development of social and physiological interventions that could reduce the burden of aging-related disease in our aging population.
