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Gene regulatory analysis of social integration and resilience during aging

衰老过程中社会融合和复原力的基因调控分析

基本信息

批准号：
10105463
负责人：
Noah Snyder-Mackler
金额：
$ 9.88万
依托单位：
ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-15 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10105463
关键词：
Gene regulatory analysis social integration

项目摘要

PARENT R00 PROJECT SUMMARY Almost half of American adults over 60 years old report being lonely, a condition that can have a major impact on health and mortality risk in later life. Adults with weak social relationships experience a 50% higher mortality rate than more socially integrated adults—an effect on par with that of smoking, obesity, or alcoholism. One explanation for this association is if better social integration increases resilience against stressful experiences, a hypothesis known as “stress buffering.” Yet despite the importance of social integration for human health, the behavioral and molecular mechanisms that mediate its potential role in stress buffering remain poorly understood, limiting its practical application to improving resilience during aging. The objective of the proposed study is to identify the genomic mechanisms that link social integration to stress sensitivity and inflammation. I hypothesize that low levels of social integration will be associated with dysregulation of the gene regulatory response to acute stress. To test this, I will leverage the advantages of studying rhesus macaques, a well-established animal model for human aging and social behavior. Work performed during the mentored phase of this award has shown that the social environment alters the epigenomic and genomic landscape of immune cells and that these changes may underlie variation in acute stress susceptibility in individuals who have more favorable vs. more adverse social environments. These findings suggest a potential mechanism, epigenomic changes, through which social adversity may accelerate the aging process. Probing how age and social experience interact to alter this mechanism will be the focus of the independent phase of this project. This project will combine studies of free-ranging macaques (Aim 1) with experimental manipulations of the social environment (Aim 2) to yield insight into the relationship between acute stress and gene regulation in a natural environment and a more controlled setting. In both contexts, I will combine genome-wide gene expression, DNA methylation, and chromatin accessibility measurements to characterize the genomic pathways associated with social integration and its relationship with the acute stress response. I will also test whether these relationships are exaggerated for older animals, and whether the presence of a close social partner can enhance resilience to psychosocial stress. At its conclusion, this project will yield a detailed understanding of how social integration impacts gene regulation in pathways that become dysregulated with age and whether social support can buffer against acute stressors at the genomic level. Together, these results will significantly advance our understanding of the mechanisms through which social integrations promotes resilience in the elderly.

PANER00项目总结几乎一半的60岁以上的美国成年人报告说他们感到孤独，这种情况可能会产生重大影响对晚年健康和死亡风险的影响。社会关系薄弱的成年人死亡率高出50% 与社会融合程度更高的成年人相比，这一影响与吸烟、肥胖或酗酒的影响相当。一对这种联系的解释是，如果更好的社会融合增加了对压力经历的弹性，一个被称为“压力缓冲”的假设然而，尽管社会融合对人类健康很重要，介导其在压力缓冲中的潜在作用的行为和分子机制仍然很差理解，限制了其实际应用，以提高在老化过程中的弹性。这项研究的目的是确定将社会融合与压力联系起来的基因机制敏感性和炎症。我推测，低水平的社会融合将与基因对急性应激的调节反应失调。为了验证这一点，我将利用研究恒河猴，这是一种成熟的人类衰老和社会行为的动物模型。工作在该奖项的指导阶段进行的研究表明，社会环境改变了免疫细胞的表观基因组和基因组景观，这些变化可能是急性压力易感性在个人谁拥有更有利的与更不利的社会环境。这些研究结果提出了一种潜在的机制，即表观基因组变化，通过这种机制，社会逆境可能会加速衰老的过程探索年龄和社会经验如何相互作用以改变这种机制将是本研究的重点。这个项目的独立阶段。本项目将联合收割机结合自由放养猕猴的研究（目标1）和社会环境（目标2），以深入了解急性应激和基因调控之间的关系，在一个自然环境和更可控的环境。在这两种情况下，我将联合收割机结合全基因组基因表达，DNA甲基化和染色质可及性测量，以表征基因组与社会融合相关的途径及其与急性应激反应的关系。我还将测试这些关系是否被夸大了老年动物，以及是否存在密切的社会关系，可以增强对心理压力的适应力。在其结论，这个项目将产生一个详细的了解如何社会融合影响基因随着年龄的增长，调节途径变得失调，以及社会支持是否可以缓冲急性基因组水平的压力源。总之，这些结果将大大促进我们对社会融合促进老年人复原力的机制。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Identifying wildlife reservoirs of neglected taeniid tapeworms: Non-invasive diagnosis of endemic Taenia serialis infection in a wild primate population.

DOI：
10.1371/journal.pntd.0005709
发表时间：
2017-07
期刊：
PLoS neglected tropical diseases
影响因子：
3.8
作者：
Schneider-Crease I;Griffin RH;Gomery MA;Dorny P;Noh JC;Handali S;Chastain HM;Wilkins PP;Nunn CL;Snyder-Mackler N;Beehner JC;Bergman TJ
通讯作者：
Bergman TJ

Insights from evolutionarily relevant models for human ageing.

来自人类衰老进化相关模型的见解。

DOI：
10.1098/rstb.2019.0605
发表时间：
2020
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
0
作者：
EmeryThompson,Melissa;Rosati,AlexandraG;Snyder-Mackler,Noah
通讯作者：
Snyder-Mackler,Noah

Social drivers of maturation age in female geladas

雌性狒狒成熟年龄的社会驱动因素

DOI：
10.1093/beheco/arac028
发表时间：
2022
期刊：
Behavioral Ecology
影响因子：
2.4
作者：
Feder, Jacob A.;Beehner, Jacinta C.;Baniel, Alice;Bergman, Thore J.;Snyder-Mackler, Noah;Lu, Amy;Jennions, ed., Michael D.
通讯作者：
Jennions, ed., Michael D.

Holistic Rehabilitation: Biological Embedding of Social Adversity and Its Health Implications.

整体康复：社会逆境的生物嵌入及其健康影响。