Mouse models for the influence of the social environment on health and aging

社会环境对健康和衰老影响的小鼠模型

• 批准号: 10512895
• 负责人: Alessandro Bartolomucci
• 金额: $ 31.13万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10512895
• 关键词: Address; Affect; Age; Aging; Algorithms; Animals; Assessment tool; Behavior; Behavioral; Biological; Biological Models; Cell Aging; Cessation of life; Cognitive; DNA Methylation; Data; Development; Disease; Early Intervention; Energy Metabolism; Epigenetic Process; Etiology; Experimental Designs; Female; Future; Genetic; Goals; Health; Human; Impairment; Individual; Intervention; Knowledge; Laboratories; Laboratory mice; Link; Longevity; Mammals; Measures; Modeling; Molecular; Mus; Natural History; Onset of illness; Pathogenicity; Phase; Physical Function; Physiological; Physiology; Prevalence; Process; Randomized; Research; Role; Shapes; Social Behavior; Social Environment; Social Functioning; Social Gradients; Social Interaction; Social Processes; Social isolation; Social support; Socioeconomic Status; Testing; Therapeutic; Time; Translating; base; burden of illness; comparative; design; doubly-labeled water; environmental enrichment for laboratory animals; flexibility; frailty; functional disability; genetic manipulation; healthspan; human old age (65+); improved; indexing; individual variation; innovation; insight; low socioeconomic status; male; mortality; mouse model; neglect; novel; predictive modeling; prevent; resilience; social; social adversity; social deprivation; social factors; social health determinants; social influence; social integration; social stress; therapy design; unethical

Summary A social gradient in health and aging is well established in humans; the greater the social connectedness and socioeconomic status (SES), the lower the burden of a plethora of diseases and mortality rate. Consistently, lack of social support and low SES are among the major negative determinants of health, increasing the prevalence and/or anticipating the onset of diseases. Unfortunately, diseases often only manifest at old age when therapeutic options and biological flexibility are limited. Additionally, the causal role of social context on aging is difficult to ascertain, requiring an experimental design in which social factors can be randomized to infer causation, which is unethical and often not feasible in humans. The evolutionary conserved role of social determinants of health and aging (SDoHA) and the ability to conduct randomized experimental designs in social mammals, offer the opportunity to reverse-translate observations made in humans to other animals. In particular, the use of laboratory mice has several advantages to study the effect of social factors on aging, including: their comparatively short lifespan when compared to other mammals enabling the completion of longevity studies in a reasonable timeframe; the ability to conduct intent-to-treat randomization designs of socio-behavioral variables; they are amenable to sophisticated genetic manipulations. However, the role of SDoHA is often neglected in biomedical aging research using mice, thus missing critical components of human aging. The objectives of this project are to: (i) develop rigorous socio-behavioral models suitable for aging studies in male and female mice; (ii) develop innovative assessment tools and a “comprehensive aging index” summarizing the global impairment in behavior, physical functions and physiology, and a that can predict functional impairment and longevity, (iii) identify social factors affecting individual variability in aging processes, and finally (iv) identify socio-behavioral intervention strategies to increase resilience. The R61 – development, proof-of-concept phase has 2 Aims. Aim 1 will identify social factors affecting the pace of aging by using a randomized design that manipulates social connectedness, social stability and social stress. We will also develop quantitative assessment tools relevant for aging research. Aim 2 will develop a “comprehensive aging index”, an algorithm which is based on quantifiable behavioral, physical and physiological changes over the lifecourse. The R33 – implementation phase has 2 Aims. Aim 3 will determine whether social rank, social instability and/or social deprivation affect lifespan in male and female mice and will implement the algorithm to predict longevity based on data collected during the lifecourse. Aim 4 will implement behavioral strategies designed to increase resilience, including social rank reversal, social integration and cognitive stimulation/environmental enrichment. At its completion, this project will develop novel experimental paradigms and assessment tools with far reaching impact to the field. It will also generate an unprecedented new knowledge on how social factors affect health trajectories and aging, and which aging process is amenable to intervention versus those that are not amenable to intervention.

概括 在人类中，健康和衰老方面的社会梯度已经建立了更大的社会联系和 社会经济地位（SES），较少的疾病和死亡率的负担较低。 在健康的主要负面决定因素中，社会支持和低SES，增加了患病率 和/或预期疾病的发作。 治疗方法和生物学是有限的，社会环境在衰老是IS IS中的因果作用。 difficalt可以确定，需要一个实验设计，其中可以随机推断社会因素 因果关系，这是不道德的，通常在人类中不可行。 健康与衰老的决定因素（SDOHA）以及在社会上进行随机实验设计的能力 哺乳动物提供了统一的统一性，可以将在人类中进行的观察到其他动物。 使用实验室小鼠有几个方面的优势来研究社会因素对衰老的影响，包括： 与其他哺乳动物相比，比较短的寿命 合理的时间范围； 它们适合复杂的遗传操作。 使用小鼠的生物医学衰老研究，因此缺少人类衰老的关键成分。 项目是：（i）开发严格的社会行为模型，适用于男性和雌性小鼠的衰老研究； （ii）开发了创新的评估工具和一个总结全球障碍的“全面动索指数” 在行为，身体功能和生理学以及可以预测功能和寿命的A中，（iii） 确定社会因素深情衰老过程中的个人变异性，最后（iv）确定社会行为 增加弹性的策略。 1将通过使用操纵社会的随机设计来确定影响衰老速度的社会因素 联系，社会稳定和社会压力。 衰老研究。 行为，物理和生理学在生命周期内发生变化。 AIM 3 Willmine男性的社会等级，社会不稳定和/或社会剥夺的感情寿命以及 雌性小鼠和意志算法在生命过程中根据数据收集器预测寿命。 AIM 4将实施旨在提高韧性，倾向的社会等级逆转，社会的行为策略 整合和认知刺激/环境丰富。 实验范式和评估工具对该领域产生了巨大影响。 关于社会因素如何影响健康轨迹和衰老的空前的新知识，以及哪些衰老 过程与干预相对于不适合干预的过程可以进行。