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

摘要

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.