Epigenetic mechanisms underlying the direct and moderating effects of social connectedness on complex diseases in aging

社会联系对衰老过程中复杂疾病的直接和调节作用的表观遗传机制

• 批准号: 10539029
• 负责人: Brea Louise Perry
• 金额: $ 54.1万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 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 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10539029
• 关键词: Acceleration; Acute; Address; Adverse effects; Affect; Age; Aging; Alcohol consumption; Alzheimer' s Disease; Alzheimer' s disease related dementia; Area; Attention; Attenuated; Behavioral; Behavioral Mechanisms; Biological; Biological Aging; Biological Markers; Biological Process; Cardiovascular Diseases; Cells; Characteristics; Chronic; Complex; DNA; DNA Methylation; Data; Dementia; Diabetes Mellitus; Discrimination; Disease; Disease Outcome; Divorce; Elderly; Empirical Research; Environmental Exposure; Epigenetic Process; Event; Exercise; Exhibits; Exposure to; Family; Frequencies; Future; Goals; Health; Health Care Costs; Health Surveys; Homeostasis; Household; Human; Human Development; Imprisonment; Individual; Inflammation; Intervention; Interview; Knowledge; Life; Life Cycle Stages; Link; Literature; Meta-Analysis; Methods; Methylation; Modeling; Morbidity - disease rate; Obesity; Onset of illness; Outcome; Pathogenesis; Pathogenicity; Pathway interactions; Pattern; Personal Satisfaction; Persons; Phenotype; Physiological; Population; Probability Samples; Process; Property; Publishing; Reporting; Research; Research Infrastructure; Research Personnel; Risk; Risk Factors; Role; Salivary; Science; Site; Smoking; Social Network; Social isolation; Stress; Stroke; Structure; Time; Tissues; United States National Institutes of Health; Variant; adverse childhood events; base; cardiometabolism; cohort; data infrastructure; density; early detection biomarkers; epigenetic marker; epigenome-wide association studies; experience; food insecurity; genomic locus; healthy aging; improved; innovation; member; middle age; mortality; mortality risk; neuropsychiatric disorder; novel; obesity risk; population health; protective effect; public health priorities; resilience; response; saliva sample; sedentary lifestyle; social; social implication; social influence; social structure; stressor; trend

PROJECT SUMMARY The goal of this project is to identify epigenetic pathways underlying the effects of social connectedness on aging-related morbidity and mortality. We propose to examine the potential pathogenic and protective consequences of individuals’ habitual patterns of interaction with members of their egocentric, or personal, social networks (i.e., their social signatures). Meta- analyses have identified beneficial effects of social connectedness on all-cause mortality that are robust and larger in magnitude than the adverse effects associated with smoking, alcohol consumption, sedentary lifestyle, and obesity. However, the biological processes underlying these patterns have received insufficient empirical study relative to behavioral mechanisms, and little attention has focused on longer-term physiological or pathogenic mechanisms. To address these gaps, we examine the implications of social signatures for DNA methylation (DNAm), a biomarker of accelerated biological aging and an early predictor of later-life onset of diabetes, cardiovascular disease (CVD), stroke, dementia, and other complex diseases. We leverage a large, omnibus health survey, the Person to Person (P2P) Health Interview Study (N≈3,050), administered face-to-face to a stratified household probability sample. As part of this effort, DNA was extracted from saliva samples (n≈2,600) for future analysis. We address the following specific aims: Aim 1 examines associations between social signatures and DNA methylation-based profiles, including epigenetic age acceleration and polyepigenetic scores. Aim 2 assesses whether social signatures attenuate documented associations between early life, mid-life, and chronic exposures to stressful conditions and DNA methylation-based profiles. Aim 3 explores associations between social signatures and targeted DNA methylation sites documented to affect risk for obesity, inflammation, Alzheimer’s disease, and other specific complex diseases associated with aging. The proposed study is interdisciplinary, combines leading-edge methods from the social and biomedical sciences, and leverages considerable existing data and research infrastructure. By increasing our understanding of the specific biological pathways underlying the effects of social connectedness that unfold over the life course, this study could help identify novel targets for earlier social or biological intervention in aging-related complex diseases.

项目摘要 该项目的目标是确定社会影响的表观遗传途径， 与年龄有关的发病率和死亡率的联系。我们建议研究 致病性和保护性后果的个人的习惯模式的相互作用， 他们以自我为中心的或个人的社交网络的成员（即，社会签名）。Meta- 分析已经确定了社会联系对全因死亡率的有益影响， 与吸烟、饮酒、 久坐不动的生活方式和肥胖。然而，潜在的生物过程 这些模式相对于行为机制没有得到充分的实证研究， 很少有人关注长期的生理或致病机制。解决 这些差距，我们研究了社会签名对DNA甲基化（DNAm）的影响， 加速生物衰老的生物标志物和糖尿病晚年发病的早期预测因子， 心血管疾病（CVD）、中风、痴呆和其他复杂疾病。我们利用 大型综合性健康调查，人对人（P2P）健康访谈研究（N = 3，050）， 管理面对面的分层家庭概率样本。作为这项工作的一部分，DNA 从唾液样本（n = 2，600）中提取用于未来分析。我们具体解决以下问题： 目的：目的1检查社会签名和DNA甲基化之间的关联 包括表观遗传年龄加速和多表观遗传评分。目标2评估 社会特征是否削弱了早期生活、中年生活和 长期暴露于压力条件和基于DNA甲基化的概况。Aim 3探索 社会签名和靶向DNA甲基化位点之间的关联记录影响 肥胖、炎症、阿尔茨海默病和其他特定复杂疾病的风险 与衰老有关。拟议的研究是跨学科的，结合了前沿的方法， 从社会和生物医学科学，并利用大量现有的数据和研究 基础设施演进通过增加我们对潜在的特定生物学途径的了解， 社会联系的影响，展现在生命历程中，这项研究可以帮助确定新的 在与衰老有关的复杂疾病中，早期社会或生物干预的目标。