Aging Leads to Altered Physiological Reactivity in Response to Repeated Social Separation Stress in a Nonhuman Primate Model

Social relationships are critical for maintaining physical health and psychological wellbeing. Since nearly 1 in 4 adults aged 65 years or older are socially isolated, there is a strong need to understand how repeated social stress negatively impacts health outcomes. Using a nonhuman primate model of social aging (i.e., marmosets), we examined whether individuals transitioning into old age ("peri-geri") or individuals who were already geriatric ("very-geri") showed differences in measures of hypothalamic-pituitary axis (HPA) activity, markers of metabolic and immune function, and reunion social behavior in response to repeated social separation challenges (SSC). We found female marmosets, especially peri-geri females, had higher HPA reactivity and better HPA recovery than male marmosets, but this difference diminished in older, very-geri marmosets. HPA activity was correlated with multiple outcomes including locomotive behavior and grooming, changes in blood glucose levels, and neutrophil counts. Moreover, marmosets who approached their partner more and were groomed less during reunions had higher cortisol levels the following day. Interestingly, we found two distinct HPA profiles among our marmosets with half showing strong HPA responses (reactors) and the other half showing little or no HPA response (non-reactors). Non-reactors had less weight gain/more weight loss; elevated levels of calcium, phosphorus, and white blood cells; and received less grooming and social contact time during reunion. Overall, old-aged marmosets who show attenuated HPA responses may have different vulnerabilities to negative health and behavioral outcomes during social stress, and male marmosets appear more likely to present with this HPA non-reactor phenotype earlier in aging.