Abstract
Allostatic load, which is characterized by the dysregulation of physiological activity across multiple systems in
the body, has been linked to an increased risk of chronic diseases such as diabetes, heart disease, and stroke.
However, the prevalence of allostatic load is not equally distributed among US subgroups, with Black adults
having higher allostatic load than White adults, particularly during middle and older age. The reasons for these
disparities are not fully understood, despite research into factors such as stressors, diet, and socioeconomic
position. Discrimination has been identified as a risk factor for allostatic load. While discrimination is
understood as a multidimensional construct that operates at multiple levels and in different social contexts, the
association between multiple forms of discrimination and allostatic load remains understudied, as well as the
underlying mechanisms by which discrimination may affect physiological function. The cellular-level processes
through which discrimination "gets under the skin" and leads to physiological dysregulation remain unclear.
This study aims to define the relationship between multiple forms of discrimination and allostatic load using
data from three large, population-based cohort studies, in order to increase the efficacy of prevention efforts
and treatment to reduce allostatic load and Black-White disparities in allostatic load. By assessing the
associations between multiple forms of discrimination (neighborhood and interpersonal) with allostatic load, the
study will quantify the extent to which discrimination explains racial disparities in allostatic load. The study will
also investigate the extent to which "Conserved Transcriptional Response to Adversity" (CTRA) gene
expression mediates the relationship between discrimination and allostatic load, as well as evaluate the
moderating effect of social integration on these associations. Overall, this study has the potential to inform the
optimization of existing clinical and place-based interventions aimed at reducing allostatic load by highlighting
the importance of addressing discrimination and identifying the timing, context, and most at-risk groups that
can benefit from these interventions to reduce health disparities.
