Developing insertable cardiac monitors to assess social and environmental effects on the autonomic stress response in a nonhuman primate model of aging

开发可插入心脏监测仪，以评估社会和环境对非人类灵长类衰老模型中自主应激反应的影响

• 批准号: 10683337
• 负责人: Elizabeth Archie
• 金额: $ 28.88万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10683337
• 关键词: Acceleration; Accelerometer; Acute; Adult; Affect; Aging; Animal Model; Animals; Autonomic nervous system; Biological Assay; Calibration; Cardiac; Cardiometabolic Disease; Chronic; Chronic stress; Data; Diabetes Mellitus; Dimensions; Electrocardiogram; Energy Metabolism; Event; Face; Famines; Glucocorticoids; Goals; Grain; Health; Heart Diseases; Heart Rate; Hour; Human; Implant; Individual; Kenya; Lead; Life; Life Cycle Stages; Life Experience; Link; Longevity; Longitudinal Studies; Measures; Mediating; Metabolic; Metabolism; Mission; Modeling; Monitor; Neurosecretory Systems; Papio; Physical activity; Physiology; Population; Poverty; Primates; Process; Prognostic Marker; Proxy; Public Health; Recovery; Research; Rest; Risk Behaviors; Shapes; Social Conditions; Social Environment; Social isolation; Stress; Testing; Time; Validation; Walking; Work; acute stress; biological adaptation to stress; cardiometabolism; cardiovascular disorder risk; cost; disorder risk; doubly-labeled water; early life adversity; environmental stressor; experience; heart rate variability; hypothalamic-pituitary-adrenal axis; mortality; neglect; nonhuman primate; obesity risk; prospective; psychosocial; response; social; social adversity; social stressor; stressor; tool

Project Summary The long reach of early life remains one of the most enduring puzzles in human health. From famine to poverty and neglect, adverse early life experiences lead to higher mortality and elevated risk for obesity, diabetes, and chronic heart disease. These effects are likely mediated, in part, by the stress response, a cascade of neuroendocrine, metabolic, and cardiac responses to challenge involving the hypothalamic– pituitary–adrenal (HPA) axis and the autonomic nervous system. In support, several leading hypotheses propose that repeated social and environmental stressors—both in early life and adulthood—cause over- activation of the stress response, chronic stress, and accelerated aging. Long-term studies of natural animal populations offer compelling models for testing these ideas because they often have fine-grained, prospective, longitudinal data on social and environmental stressors from individuals across the life course. However, natural animal models also face considerable challenges in measuring multiple facets of the stress response: most are constrained to measuring glucocorticoids (GCs) as the sole measure of stress responses, reflecting just one aspect of the HPA axis with no information on autonomic responses. This limitation has led many to call for expanded tools to measure stress responses in natural animal models of aging. Our objectives in this proposal are to: (1) expand the tools for measuring the cardiometabolic consequences of stress in natural animal models by validating insertable cardiac monitors (ICMs) with accelerometry to measure heart rate, heart rate variability, and physical activity; and (2) test the social and environmental drivers of the autonomic stress response and its metabolic consequences. We will develop and validate ICMs using captive baboons at the Institute of Primate Research in Kenya, and a well-studied, natural population of baboons in Amboseli, also in Kenya. Prior work in Amboseli has already shown that an accumulation of harsh conditions in early life and social isolation in adulthood exert profound effects on adult mortality, setting the stage to probe the stress responses underlying these links. While early life adversity and social isolation lead to elevated GCs in adulthood, and animals with high lifelong GCs have lower survival, GCs do not mediate the link between early adversity and life span. Gaining a broader perspective on individual stress responses and their consequences is an essential next step. The results will contribute the first prospective, longitudinal data in any species to understand how early life adversity and adult social conditions interact to shape acute autonomic stress responses, chronic stress, and energy expenditure. This study will provide a direct link between socio-environmental circumstances, stress responses, and adult health, helping to identify key targets to mitigate the effects of stress over the life course on aging.

项目摘要 早期生命的漫长范围仍然是人类健康中最持久的难题之一。从饥荒到 贫穷和忽视，不利的早期生活经历会导致更高的死亡率和对物体的风险升高， 糖尿病和慢性心脏病。这些作用可能部分是由应力反应介导的 神经内分泌，代谢和心脏反应的级联反应，涉及下丘脑 - 垂体 - 肾上腺（HPA）轴和自主神经系统。在支持中，几个主要的假设 提出重复的社会和环境压力源（无论是在早期和成年期）是否导致过度的 应力反应，慢性应激和加速衰老的激活。天然动物的长期研究 人群提供令人信服的模型来测试这些想法，因为它们通常具有细粒度，潜在的， 整个生活过程中个人的社会和环境压力源的纵向数据。然而， 天然动物模型在测量压力反应的多个方面也面临着巨大的挑战： 大多数限制在测量糖皮质激素（GC）作为应力反应的唯一量度，反映 HPA轴只有一个方面，没有关于自主响应的信息。这个限制导致许多人 呼吁扩大工具来衡量自然动物衰老模型中的压力反应。 我们在此提案中的目标是：（1）扩展用于测量心脏代谢的工具 自然动物模型中压力的后果是通过验证可插入的心脏监视器（ICMS） 加速度计测量心率，心率变异性和身体活动； （2）测试社交和 自主压力反应的环境驱动因素及其代谢后果。我们将发展和 使用肯尼亚灵长类动物研究所的圈养狒狒验证ICMS，并且是一个良好的，自然的 也在肯尼亚的Amboseli的狒狒人口。 Amboseli的先前工作已经表明 在早期生活中的危害条件积累，成年后的社会隔离对成人产生深远影响 死亡率，设定阶段以探测这些联系的压力反应。而早期的冒险和 社会隔离导致成年后的GC升高，终生GC的动物的生存率较低，GCS 不要调解早期广告和寿命之间的联系。对个人有更广泛的看法 压力反应及其后果是下一步。结果将为第一个贡献 任何物种中的前瞻性，纵向数据，以了解早期生活和成人社会状况如何 相互作用以塑造急性自主压力反应，慢性应激和能量消耗。这项研究会 在社会环境，压力反应和成人健康之间提供直接联系 确定关键目标以减轻压力对生活过程对衰老的影响。