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

项目总结 这个项目的目标是确定潜在的社会影响的表观遗传途径。 与老龄化相关的发病率和死亡率的关联性。我们建议研究一下潜在的 个人与人相互作用的习惯性模式的致病和保护后果 他们以自我为中心或个人的社交网络的成员(即他们的社交签名)。Meta- 分析发现，社会联系对全因死亡率的有利影响是 比吸烟、酗酒带来的不良影响更强大、更强大 消费、久坐不动的生活方式和肥胖。然而，潜在的生物过程 关于行为机制，这些模式没有得到足够的实证研究 很少有人关注更长期的生理或致病机制。致信地址 在这些差距中，我们研究了社会签名对DNA甲基化(DNaM)的影响，a 加速生物衰老的生物标记物和糖尿病晚年发病的早期预测因子， 心血管疾病(CVD)、中风、痴呆症和其他复杂疾病。我们利用 大型综合性健康调查，个人对个人(P2P)健康访谈研究(N≈3,050)， 对分层的家庭概率样本进行面对面的调查。作为这一努力的一部分，DNA 是从唾液样本(n≈2,600)中提取的，以供将来分析。我们解决了以下具体问题 目标：目标1研究社会特征和DNA甲基化之间的关系 概况，包括表观遗传年龄加速和多表观遗传得分。AIM 2评估 社会签名是否削弱了早年、中年和 长期暴露在应激条件下和基于DNA甲基化的图谱。《目标3》探索 社会特征和目标DNA甲基化位点之间的关联被记录为影响 肥胖、炎症、阿尔茨海默病和其他特定复杂疾病的风险 与衰老相关的。建议的研究是跨学科的，结合了前沿方法。 来自社会和生物医学科学，并利用大量现有数据和研究 基础设施。通过增加我们对潜在的特定生物途径的理解 在生命过程中展现的社会联系的影响，这项研究可以帮助识别小说 衰老相关复杂疾病早期社会或生物干预的目标。

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.