Biological Underpinnings of Socioeconomic Differentials in Health and Mortality

摘要 该项目将使用来自健康和退休研究(HRS)的独特的新数据资源来阐明 生命过程中社会劣势“深入”并产生影响的多种生物学途径 随后的发病率和死亡率。我们将研究社会逆境和多重危机之间的联系 与生物衰老基本过程有关的综合措施，包括临床生理指标 状态、免疫系统功能、端粒磨损、线粒体耗竭、DNA甲基化和基因 表达，以了解那些社会经济地位低的人“年龄”的机制 比具有更高SES的人更快。这个项目的独特性在于广度和深度 描述衰老的一些基本机制的生物学指标 在具有全国代表性的人群中进行了检查，有能力表征SES差异。 我们预计，较低的社会经济地位(SES)，以及相关的应激性生活事件、不良心理 不健康的行为会与更差的生理状态、免疫功能、 甲基化特征、不利表达、更多的线粒体耗竭和更短的端粒长度 按时间顺序排列的年龄。虽然任何年龄的低SES和伴随的生活环境预计都是 与晚年生物学有关，从童年开始并贯穿始终的累积社会劣势 正如我们预计的那样，生命在增加不良生物标志物方面存在乘性关联 生物过程更多地受到童年环境的影响，而其他生物过程则更受现代环境的影响 情况。我们将研究低SES的情感、财务和心理成本之间的关联 早期和晚期的生命具有生物学结果，并假设生活的这些不同方面的影响将 随时间和域的不同而不同。我们还将确定遗传和社会、心理和环境 缓冲因素，将减少低SES与不良生物学特征的关联。 该项目的成果将是确定一套全面综合的措施， 描述从社会逆境到健康状况不佳的生物学途径，并从生物学层面解释为什么 社会上处于不利地位的个人面临与老龄化相关的发病率和死亡率后果的更大风险。 识别影响衰老速度的多种社会和生物机制将增强我们的 了解健康差距的根本原因及其产生的生命周期过程。 这项工作将大大增加我们对易感因素(细胞和分子)如何 变化、免疫功能恶化和生理特征)和诱发因素 (社会经济地位、心理社会和环境应激源以及健康行为)共同影响年龄- 相关健康状况(与年龄相关的发病率和死亡率)。

Abstract This project will use a unique new data resource from the Health and Retirement Study (HRS) to elucidate multiple biological pathways through which life course social disadvantage “gets under the skin” and influences subsequent morbidity and mortality. We will examine the association between social adversity and multiple composite measures related to basic processes of biological aging including clinical indicators of physiological status, immune system functioning, telomere attrition, mitochondrial depletion, DNA methylation, and gene expression in order to understand the mechanisms through which those of low socioeconomic status (SES) “age” at a faster rate than persons with higher SES. The uniqueness of this project resides in the breadth and depth of the biological indicators which characterize some of the basic mechanisms of aging and have not been examined in a nationally representative population with ability to characterize SES differences. We expect that low socioeconomic status (SES), and related stressful life events, adverse psychological states, and poor health behaviors will be associated with worse physiological status, immunological functioning, methylation profile, adverse expression, more mitochondrial depletion, and shorter telomere length at a given chronological age. While low SES and accompanying life circumstances at any age are expected to be associated with late life biology, cumulative social disadvantage beginning in childhood and sustained throughout life is expected to have a multiplicative association in increasing adverse biological markers as we expect some biological processes to be more influenced by childhood circumstances and others by more current circumstances. We will examine the association of emotional, financial, and psychological costs of low SES in early and later life with biological outcomes and hypothesize that the effect of these different aspects of life will vary with timing and domain. We will also identify both genetic and social, psychological and environmental buffering factors that will reduce the association of low SES with adverse biological profiles. The outcome of this project will be the identification of a comprehensive-integrated set of measures that characterize the biological pathway from social adversity to poor health and “explain” at a biological level why socially disadvantaged individuals are at greater risk of aging-related morbidity and mortality outcomes. Identifying multiple social and biological mechanisms that influence the pace of aging will enhance our understanding of the underlying causes of health disparities and the lifecycle processes by which they arise. This work will increase substantially our understanding of how predisposing factors (cellular and molecular changes, deterioration in the immune function, and physiological characteristics) and precipitating factors (socioeconomic status, psychosocial and environmental stressors, and health behaviors) together influence age- related health conditions (age-related morbidity and mortality).