Social Disadvantage and Its Impact on Pathogen Burden and Immune Dysfunction Across the Life Course

社会劣势及其对整个生命过程中病原体负担和免疫功能障碍的影响

• 批准号: 10605356
• 负责人: Grace A Noppert
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605356
• 关键词: 18 year old; Acceleration; Aging; Back; Biological Markers; Biological Process; Cessation of life; Child; Childhood; Chronic; Chronic Disease; Cohort Studies; Cytomegalovirus; Data; Development; Disease; Disparity; Disparity population; Elderly; Epidemiology; Equation; Event; Hepatitis A Virus; Hepatitis B Virus; Herpesvirus 1; Immune System Diseases; Immune system; Impaired cognition; Individual; Infection; Inflammation; Knowledge; Life; Life Cycle Stages; Life Experience; Link; Measures; Mediating; Mediation; Mediator; Mentors; Methods; Modeling; Morbidity - disease rate; Motion; Onset of illness; Pathway interactions; Physical Function; Physiological; Poverty; Process; Reproducibility; Research; Role; Sampling; Sociology; Stress; Testing; Thymus Gland; Training Activity; Work; age related; assault; career; chronic infection; design; disability; experience; health disparity; immunosenescence; improved; indexing; innovation; low socioeconomic status; middle age; mortality; novel; pathogen; physical abuse; population health; programs; senescence; social disparities; stressor; systemic inflammatory response

Project Summary 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.

Project Summary 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.