Epigenetic Age Acceleration Impacts Racial and Neighborhood Disparities in Chronic Low Back Pain

摘要 慢性下腰痛(CLBP)是一种与年龄相关的疾病，影响超过60%的老年人，其成本高达 每年3150亿美元。年龄相关疾病的负担，包括慢性下腰痛，对黑人的影响不成比例 美国人和高贫困社区的居民。高度贫困的社区有很高的 贫困集中，缺乏就业和质量等以社会经济资源为基础的指标 住房。令人不安的是，高度贫困的居民的预期寿命可能会缩短长达20年 邻里关系。然而，作为美国黑人生活的生物机制，高度剥夺 社区，更糟糕的慢性LBP结果，以及缩短的预期寿命仍然不清楚。表观遗传变化 例如DNA甲基化(DNaM)将环境暴露与基因表达联系起来，并可能影响疾病 风险。这种表观遗传修饰可能会影响个人的生物学(表观遗传)年龄，这可能是 用dNaM模式估计。尽管表观遗传年龄加速(EPAA)强烈预测死亡率和 EPAA在包括慢性疼痛在内的许多与年龄相关的情况下被观察到，但目前尚不清楚EPAA是否可以 解释社区剥夺与cLBP中种族差异之间的关系。我们的中央 假设黑人和高贫困社区的居民承受着更高水平的压力 这会对身体造成“磨损”，并在表观遗传上加速衰老。我们的长期目标是提高年龄- 通过揭示基于地点(例如，地理)的年龄差距的生物学机制-- 相关的慢性疾病。这项研究的目的是考察EPAA与 邻里剥夺、种族和cLBP。使用汉纳姆的方法计算表观遗传年龄，我们将 检查50名黑人和50名白人男性和女性的EPAA，包括等量的cLBP和无疼痛的 控制。目的1：探讨EPAA合并慢性LBP与病情严重程度的关系。目标2：达到 研究EPAA与邻里剥夺、种族和性别之间的联系。目标3：探索 EPAA是否在邻里剥夺与慢性下腰痛严重程度之间的关系中起中介作用。我们的发现 将对健康差异研究产生重大影响，因为它指出了一条发病和病程的途径 与年龄相关的疾病。

ABSTRACT Chronic low back pain (cLBP) is an age-related condition that affects over 60% of older adults and costs up to $315 billion annually. The burden of age-related diseases, including cLBP, disproportionately impacts Black Americans and residents of high deprivation neighborhoods. High deprivation neighborhoods have a high concentration of poverty and lack socioeconomic resource-based indicators such as employment and quality housing. Disturbingly, life expectancy may be up to 20 years shorter for residents of high deprivation neighborhoods. Yet, the biological mechanisms that link living as a Black American, high deprivation neighborhoods, worse cLBP outcomes, and shortened life expectancy remain unclear. Epigenetic changes such as DNA methylation (DNAm) link environmental exposures to gene expression and may affect disease risk. Such epigenetic modifications may affect an individual’s biological (epigenetic) age, which can be estimated with DNAm patterns. Though epigenetic age acceleration (EpAA) strongly predicts mortality and has been observed in many age-related conditions, including chronic pain, it remains unclear whether EpAA can explain the relationship between neighborhood deprivation and racial disparities in cLBP. Our central hypothesis is that Blacks and residents of high deprivation neighborhoods experience higher levels of stress that exert “wear and tear” on the body and epigenetically accelerate age. Our long-term goal is to improve age- related conditions by uncovering biological mechanisms for place-based (e.g., geographic) disparities in age- related chronic conditions. The objective of this study is to examine the relationships between EpAA with neighborhood deprivation, race, and cLBP. Using Hannum’s approach for epigenetic age calculation, we will examine EpAA from 50 Black and 50 White men and women, including equal numbers of cLBP and pain-free controls. Aim #1: To investigate the relationship between EpAA with cLBP and status and severity. Aim #2: To examine the associations between EpAA with neighborhood deprivation, race, and sex. Aim #3: To explore whether EpAA mediates the relationship between neighborhood deprivation and cLBP severity. Our findings will significantly impact health disparities research by pointing towards one pathway for the onset and course of age-related conditions.