Contextual and Health Behavior Effects on Epigenetic Aging Among African Americans

摘要：有大量证据表明早期应激与加速老化有关，但可能的机制 （介体）解释这种效应的机制知之甚少。同样，持续的压力对年轻人的影响 成年期对加速衰老的影响在很大程度上是未知的。由于缺乏关于机制的资料， 和影响的时间，现有的研究是有限的，因为它主要集中在白色样本-尽管 事实上，黑人在几乎所有类型的疾病中的发病率都明显高于其他种族/族裔群体， 慢性疾病，以及炎症的大多数标志物，和表观遗传衰老（epi-A）-即，的差异 根据DNA甲基化的表观遗传学变化，在实际年龄和生物学年龄之间。拟议 研究的目的是检查：a）影响黑人加速衰老的因素，特别是经济和种族， 相关的压力;和B）调解人和调解人的作用，可能是预防的有用目标 干预措施，如物质使用和不良饮食，以及保护因素。 当前调查的重点是测试加速老化的替代途径， 以及后来的压力源一种途径关注压力对潜在不健康行为的影响（例如，物质 使用，饮食），这反过来可能会引起慢性疾病的老化。这种可能性得到以下证据的支持： 压力性生活事件，特别是与歧视有关的事件，可以预测生活方式的选择。相反，压力影响 也可能通过改变糖皮质激素系统的功能来加速衰老。或者，这两种途径可能是 相互关联此外，我们专注于扩大什么是已知的范围内的压力， 最关键的发育时期，以及保护因素对epi-A的影响程度。解决 一个重要的限制，以前的研究，我们将有可靠的，敏感的生物标志物吸烟，大麻， 酒精使用和两个时间点的饮食以及人口普查跟踪和父母报告的压力源指数 在多个时间点，允许和我们补充自我报告的措施，并检查模型更严格 并且具有比以前可能的更高的精度。 拟议的研究将集中在470名年轻人谁是一个更大的（N=889）小组研究的一部分，黑色 家庭和社区健康研究。FACHS跟踪了一组来自美国的“目标”参与者， 年龄在10至28岁之间，沿着的还有他们的父母和家庭成员。通过使用Illumina表征甲基化， 对于年轻成年期的两个时间点（28和33），我们将能够确定epi-A的变化;即， 加速老化在青年时期的可塑性程度。使用现有的自我和 父母对各种压力源的报告--来自8波数据，沿着经过充分验证的表观遗传生物标志物 epi-A，吸烟和饮酒，我们将能够利用现有的非常丰富的前瞻性FACHS 数据集，包括其关于压力，保护因素，物质使用和应对的信息，目标是 为预防性干预研究提供信息，这些研究可以解决健康老龄化差距的根源。

ABSTRACT: Considerable evidence exists linking early stress to accelerated aging, but potential mechanisms (mediators) accounting for this effect are poorly understood. Likewise, the impact of continuing stress in young adulthood on accelerated aging is largely unknown. Compounding the lack of information regarding mechanisms and timing of effects, available research is limited because it has focused mostly on White samples -- in spite of the fact that Blacks have significantly higher rates than other racial/ethnic groups of almost every type of chronic illness, as well as most markers of inflammation, and epigenetic aging (epi-A) —i.e., the difference between chronological age, and biological age, based on epigenetic changes in DNA methylation. The proposed research is designed to examine: a) factors that affect accelerated aging in Blacks, especially economic and race- related stress; and b) the role of mediators and moderators that may be useful targets for preventive interventions, such as substance use and poor diet, and also protective factors. A focus of the current investigation is testing alternative pathways to accelerated aging attributable to early and later stressors. One pathway focuses on stressor effects on potentially unhealthy behavior (e.g., substance use, diet) that may, in turn, give rise to chronic diseases of aging. This possibility is supported by evidence that stressful life events, especially those linked to discrimination, predict life style choices. Conversely, stress effects may also accelerate aging by altering functioning of the glucocorticoid system. Or, the two pathways may be interrelated. In addition, we focus on expanding what is known about the range of stressors within a given developmental period that are most critical, and the extent to which protective factors affect epi-A. Addressing an important limitation of prior research, we will have reliable, sensitive biomarkers of smoking, marijuana, alcohol use, and diet available at two time points as well as census track and parent report indices of stressors at multiple time points, allowing and us to supplement self-report measures and examine models more rigorously and with greater precision than has previously been possible. The proposed research will focus on 470 young adults who are part of a larger (N=889) panel study of Black families, the Family and Community Health Study. FACHS has followed a cohort of “target” participants from ages 10 to 28, along with their parents and family members. By characterizing methylation using the Illumina Epic array for two time points in young adulthood (28 and 33), we will be able to determine change in epi-A; i.e., the extent to which accelerated aging continues to be malleable in young adulthood. Using existing self- and parental reports of a variety of stressors-- from 8 waves of data, along with well-validated epigenetic biomarkers of epi-A, smoking, and drinking, we will be able to leverage the exceedingly rich existing prospective FACHS dataset, including its information on stress, protective factors, substance use, and coping, with the goal of informing preventive intervention research that can address the sources of disparities in healthy aging.