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

Award Number: K99AG062749
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/15/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2021

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Social Disadvantage and Its Impact on Pathogen Burden and Immune Dysfunction 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = -$34,398 )
2021	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	001	3	1/15/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$83,924
2021	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	2	1/15/2021	NON-COMPETING CONTINUATION	-$83,924
2021	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	005	3	7/21/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$34,398
2021	2020	REGENTS OF THE UNIVERSITY OF MICHIGAN	503 THOMPSON ST	ANN ARBOR	MI	48109	WASHTENAW	USA	Aging Research	004	3	5/13/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$46,134
2021	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	003	2	5/13/2021	NON-COMPETING CONTINUATION	-$36,326
2021	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	002	1	5/13/2021	NEW	-$9,808
														Subtotal = -$34,398

Issue Date FY: 2020 ( Subtotal = $120,250 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	2	4/15/2020	NON-COMPETING CONTINUATION	$120,250
														Subtotal = $120,250

Issue Date FY: 2019 ( Subtotal = $120,250 )
2019	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Aging Research	000	1	8/21/2019	NEW	$120,250
														Subtotal = $120,250

Grand Total All Awards = $206,102

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

Award Number: K99AG062749

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/15/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2021

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