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，包括 大约每四个美国居民中就有一个。根据皮尤研究中心的数据，大约26% 的老年人独居。虽然孤独并不一定与独居相关，但更多的 超过40%的老年人经常感到孤独。孤独被认为会加速 老年人的认知能力下降，可能是通过糖皮质激素水平升高和 增加炎症。有一个“巨大的未得到满足的治疗需求”的发展 认知疗法治疗与衰老相关的神经认知障碍 包括痴呆症和阿尔茨海默病。识别动物模型的特征 可能有助于这种认知疗法的发展将具有重大意义 冲击力。普通的绒猴有望成为一种重要的非人类灵长类动物模型 年龄相关疾病的研究。这项研究的重点是健康的大脑老化，而 与正常衰老相关的社会、神经内分泌和血管贡献 疾病状态。将使用标准化的认知评估来确定人口的特征 来定义哪些人认知老化好，哪些人认知老化差。以下变量的可能性 作为认知老化结果的决定因素，将被建模：性别、社会历史、当前 住房状况、脑血流(成像评估)和髓鞘形成。目标1将专注于 关于评估社会支持是否缓冲压力对认知和心理健康的影响 衰老过程中的神经内分泌功能。对一段分离时间的实验操纵 长期的配对，然后是重聚，将使我们能够研究社会缓冲对认知的作用 并考察社会支持质量如何影响对HPA轴的认知和调节。 目标2将专注于确定血管对衰老的贡献。我们将评估认知能力 老年人运动功能和脑血流量的动脉自旋标记研究 绒猴。我们预计认知结果将与脑血流量和脑功能呈正相关 血管密度。目标3将确定脑白质完整性的变化是否与 有认知功能障碍。本研究的成果将为本研究提供新的见解和更深层次的认识 了解社会应激和神经内分泌紊乱在年龄相关性疾病中的作用 认知功能障碍。我们预计，确定这些联系将从根本上推动 在衰老的研究中，可能会推进绒猴作为一种高度 这些条件的转换模型。

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.