Project Summary Social relationships are crucially important to human health. The effects of social relationships on healthy aging are seen in several systems, including the cardiovascular system, metabolism, emotion, and cognitive function. The effects of social isolation and loneliness have been shown to independently increase risk for stroke, heart disease, and overall mortality. High quality social support, in contrast, can play a positive role in healthy aging including reducing metabolic syndrome and adverse cardiovascular outcomes. Long-term partnerships (such as marriage) are the primary close relationship in many adults, but other types of relationships such as sibling relationships, other family relationships, and friendships, may also support healthy aging. Prairie voles are an excellent rodent model of social relationships, in that they show classic behavioral characteristics of an attachment bond: adult males and females form pair bonds, which are characterized by a preference for the familiar partner, distress upon separation, and the ability of the partner to provide a social buffer against stress. These behavioral characteristics in prairie voles provide researchers with the ability to examine the effects of specific types of affiliative relationships (pair mates, siblings, parent-offspring) in adult males as well as in females. The hormone oxytocin has been established as a foundational mechanism in the neurophysiology of relationship formation, relationship quality and partner loss. Its secretion is stimulated by a wide variety of social stimuli, including social touch, sex and social stress. Its receptor is widespread throughout the body. As such, it presents a potential unifying mechanism for organismal-scale effects of social relationships on the brain and the body. Here we will examine how long-term social relationships influence cardiac, metabolic, cognitive and emotional health across the lifespan. Our general approach is to use prairie voles, both males and females, in differing social conditions (pair-bonded, housed with same-sex sibling, or isolated) to examine the effects of presence of a relationship, type of that relationship, and quality of that relationship on cardiac and metabolic health, behavioral and cognitive health, and longevity. We will longitudinally assess measures of cardiac, metabolic, behavioral, and cognitive function at three timepoints: 6, 18, and 24 months of age. We will assess changes in the OT system across aging, on both brain and peripheral tissues (heart, adipose tissue, and skeletal muscle). Finally, we will explore how relationships change over time, and how loss of a partner affects healthy aging.