The process of aging often leads to increased disability, loss of physical functioning, cognitive decline, and development of multiple chronic diseases. One critical driver of this process is senescence of the immune system, or immunosenescence, which is known to be associated with chronic inflammation. However, emerging evidence also points to immune dysfunction resulting from continual assault on the immune system by multiple persistent infections. Together, these infections and resulting immune dysfunction set in motion a cascade of events leading to accelerated immunosenescence. Accelerated immunosenescence may then be a driver of health disparities later in life. New research suggests disparities in immune dysfunction across the life course can be linked to social disadvantage extending back to childhood. A critical knowledge gap is how early-life social disadvantage accelerates immunosenescence through immune dysfunction. The objective of the proposed research is to explore pathogen burden as a critical mediator in the pathway from childhood social disadvantage to accelerated aging, as measured by inflammation and immune dysfunction.
The first objective of this project is to define the association between childhood social disadvantage and pathogen burden across the life course. Childhood social disadvantage is defined by both low socioeconomic status and experiences of stressors, such as parental death or physical abuse, before 18 years of age. Individuals experiencing higher levels of social disadvantage in childhood should have increased levels of pathogen burden throughout the life course.
Defining the association between pathogen burden and immune system dysfunction and inflammationis the second objective of this project. Grace Noppert will do this first by testing the association between pathogen burden and inflammation in existing cohort studies and then test the association between pathogen burden and immune dysfunction longitudinally.
The third objective is to examine the degree to which the association between childhood social disadvantage and inflammation/immune dysfunction is mediated by pathogen burden .
At its conclusion, this project will extend our knowledge of the aging process early in the life course, specifically how childhood social disadvantage can induce accelerated aging through the mechanism of pathogen burden and amplify disparities in aging. Ultimately, this will work will inform our understanding of modifiable processes that cause disease, disability, and mortality across the life course.