Marmosets as a Model for Understanding Social, Neuroendocrine, and Vascular Contributions to Cognitive Aging

项目摘要 预计到2060年，65岁以上的美国居民人数将达到9820万，其中 大约四分之一的美国居民。根据皮尤研究中心的数据， 老年人独自生活。虽然孤独并不一定与独居有关，但更多的是 超过40%的老年人经常感到孤独。孤独症被认为会加速 老年人认知能力下降，可能通过糖皮质激素水平升高介导， 增加炎症。有一个"巨大的未满足的治疗需求"的发展， 用于治疗与衰老相关的神经认知障碍的认知治疗学 包括痴呆症和老年痴呆症。识别动物模型的特征， 可能有助于这种认知治疗的发展， 冲击普通绒猴有望成为一种重要的非人类灵长类动物模型， 对与年龄有关的疾病的研究。这项研究的重点是健康的大脑老化， 社会，神经内分泌和血管的贡献与正常老化，而不是 疾病状态。将使用标准化认知评估对人群进行表征 来定义那些认知老化程度好的人和认知老化程度差的人。以下变量的可能性 作为认知老化结果的决定因素，将建模：性别，社会历史，当前 住房条件、脑血流量（成像评估）和髓鞘形成。目标1将重点 评估社会支持是否缓冲了压力对认知和 衰老过程中的神经内分泌功能一个实验性的操纵一段时间的分离， 一个长期的配对，然后重新组合，将使我们能够研究社会缓冲对认知的作用 探讨社会支持的质量对HPA轴的认知和调节的影响。 目标2将集中于确定血管对衰老的贡献。我们将评估认知 动脉自旋标记法测定老年人的运动能力和脑血流量 绒猴我们预计认知结果将与CBF和大脑正相关 血管密度目标3将确定白色物质完整性的变化是否与 认知功能障碍本研究的结果将有助于新的见解和更深层次的 了解社会压力和神经内分泌干扰在与年龄相关的 认知功能障碍我们预计，确定这些联系将从根本上推动 研究衰老的研究，并可能推进建立绒猴作为一个高度 这些条件的转化模型。

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.