Project Summary The world’s population is aging, which brings about huge scientific challenges. Since the biological process of aging is by far the greatest risk factor for most chronic diseases, understanding the molecular and cellular mechanisms by which aging leads to these conditions is of vital importance to increase the health span of older adults. Aging results in several structural and functional changes in the immune system and is clinically associated with increases in the frequency and severity of infectious diseases and incidences of cancer, chronic in inflammatory disorders, and autoimmunity. This general dysregulation in immune system function is referred to as immunesenescence. Immunosenescence is a multifactorial and dynamic complex phenomenon, which is shown as a lengthy adjusting and remodeled process existing in immune system during lifespan. However, the mechanisms under-lying age-associated dysregulated immunity are still incompletely understood. This proposal investigates a new perspective on immune cell markers and function with age across NHP species with differing lifespans. In addition, we will examine the relationship between immune aging and neurodegenerative biomarkers and cognition and compare these relationships across the NHP species. These studies will help determine the role the immune system plays in longevity, neurodegeneration and cognitive decline, which may allow researchers to develop and test immuno-restorative approaches with the goal of improving longevity in humans.