Marmosets as a Model for Understanding Social, Neuroendocrine, and Vascular Contributions to Cognitive Aging - Project Summary The number of U.S. residents over age 65 is projected to be 98.2 million by 2060, comprising approximately 1 in 4 U.S. residents. According to the Pew Research Center, approximately 26% of older adults live alone. While loneliness does not necessarily correlate with living alone, more than 40% of seniors regularly experience loneliness. Loneliness is thought to accelerate cognitive decline in older adults, possibly mediated through rising glucocorticoid levels and increasing inflammation. There is a “great unmet therapeutic need” for the development of cognitive therapeutics for the treatment of neurocognitive disorders associated with aging including dementias and Alzheimer’s disease. Identifying characteristics of animal models that may contribute to the development of such a cognitive therapeutic would have significant impact. Common marmosets are poised to become an important nonhuman primate model in the study of age-related disease. The focus of this research is healthy brain aging, and the social, neuroendocrine, and vascular contributions associated with normal aging rather than disease states. The population will be characterized using standardized cognitive assessments to define those that have good vs poor cognitive aging. The likelihood of the following variables as determinants of cognitive aging outcomes will be modeled: sex, social history, current housing condition, cerebral blood flow (imaging assessments), and myelination. Aim 1 will focus on assessing whether social support buffers the effects of stress on cognitive and neuroendocrine function during aging. An experimental manipulation of a period of separation of a long-term pair, then reunion, will allow us to investigate the role of social buffering on cognition and examine how quality of the social support affects cognition and regulation of the HPA axis. Aim 2 will focus on identifying vascular contributions to aging. We will assess cognitive performance and cerebral blood flow (CBF) by arterial spin labeling in aged and geriatric marmosets. We expect cognitive outcomes will be positively correlated with CBF and brain vascular density. Aim 3 will determine whether changes in white matter integrity are associated with cognitive dysfunction. The results of this study will contribute novel insights and deeper understanding of the role of social stress and neuroendocrine disruption in age-associated cognitive dysfunction. We anticipate that identifying these links will fundamentally advance research in the study of aging, and may advance the establishment of the marmoset as a highly translational model of these conditions.
