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

摘要 慢性腰痛（cLBP）是一种与年龄相关的疾病，影响超过60%的老年人， 每年3150亿美元。包括cLBP在内的年龄相关疾病的负担对黑人的影响不成比例 美国人和高贫困社区的居民。贫困程度高的社区 贫困集中，缺乏基于社会经济资源的指标，如就业和质量 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20年 邻里关系然而，作为一个美国黑人， 社区，更糟糕的cLBP结果和预期寿命缩短仍不清楚。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体的生物学（表观遗传）年龄，这可能是遗传学上的。 用DNAm模式估计。虽然表观遗传年龄加速（EpAA）强烈预测死亡率， 在许多与年龄相关的疾病中观察到，包括慢性疼痛，目前尚不清楚EpAA是否可以 解释cLBP中邻里剥夺和种族差异之间的关系。我们的中央 一个假设是，黑人和高度贫困社区的居民经历了更高水平的压力 对身体造成“磨损”并在表观遗传学上加速衰老。我们的长期目标是改善年龄- 通过揭示基于场所的生物学机制（例如，年龄差距- 相关的慢性病。本研究的目的是检查EpAA与 邻里剥夺、种族和cLBP。使用Hannum的方法计算表观年龄，我们将 检查来自50名黑人和50名白色男性和女性的EpAA，包括相同数量的cLBP和无痛 对照目的#1：研究EpAA与cLBP之间的关系以及状态和严重程度。目标2： 研究EpAA与邻里剥夺，种族和性别之间的联系。目标#3：探索 EpAA是否介导了邻里剥夺与cLBP严重程度之间的关系。我们的研究结果 将对健康差异研究产生重大影响，指出一条发病和病程的途径， 与年龄有关的条件。

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.