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. To test this hypothesis, I will first define the association between childhood social disadvantage and pathogen burden across the life course (Aim 1). 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. I hypothesize that individuals experiencing higher levels of social disadvantage in childhood will have increased levels of pathogen burden throughout the life course. I will then define the association between pathogen burden and immune system dysfunction and inflammation (Aim 2). I will do this first by testing the association between pathogen burden and inflammation in existing cohort studies. I hypothesize that higher levels of pathogen burden will be associated with increased inflammation. I will then test the association between pathogen burden and immune dysfunction longitudinally. I hypothesize that those experiencing higher levels of childhood social disadvantage will experience increased immune dysfunction over the life course. Lastly, I will examine the degree to which the association between childhood social disadvantage and inflammation/immune dysfunction is mediated by pathogen burden (Aim 3). I hypothesize that pathogen burden will partially mediate the relationship between childhood social disadvantage and immune dysfunction and infllammation. At its conclusion, this project will yield an expansion of 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.

Public Health Relevance

Disparities in aging persist despite robust efforts to ameliorate them. Sociobiological processes beginning in childhood are increasingly being examined as critical drivers of these disparities. This project seeks to explore the impact of early life experiences of poverty and stress on later life inflammation and immune dysfunction, with a specific focus on infectious burden as a key mediator of these processes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Career Transition Award (K99)
Project #
1K99AG062749-01A1
Application #
9822065
Study Section
Neuroscience of Aging Review Committee (NIA)
Program Officer
Karraker, Amelia Wilkes
Project Start
2019-09-01
Project End
2021-04-30
Budget Start
2019-09-01
Budget End
2020-04-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599