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The Scars of Stress: Injury and Aging of African Killifish

Award Number: R21AG104695
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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The Scars of Stress: Injury and Aging of African Killifish - PROJECT SUMMARY Aging is the evolutionarily conserved decline of physiological and cognitive function over the organism's lifespan. While research using model organisms in optimized lab conditions has identified many aging-associated signaling pathways, much less is known about how a life history of stress contributes to intrinsic aging and affect aging-associated signaling pathways. The consequences for injury are well established and include local acute effects (activation and migration of immune cells, induction of immune response genes, tissue repair mechanisms such as stem cell activation, and epigenetic changes) as well as systemic long-term effects (chronic inflammation, scarring and long-term epigenetic changes). Here we propose to investigate how a life history of physical trauma contributes to aging and markers of aging, including inflammatory response and epigenetic markers. Our over-arching hypothesis is that a life history of injury stress will accelerate aging. We will test this hypothesis using a powerful, genetically tractable model organism, N. furzeri or African killifish. African killifish are an exciting new model for aging research given their short natural lifespan (4-6 months). Testing this hypothesis would be expensive, labor-intensive, and time-prohibitive in any other vertebrate model. First, if a life history of injury accelerates aging, then we predict that injury survivors will exhibit earlier onset and faster progression of aging markers than uninjured controls. We will test whether single or multiple exposures to different types of injury stress during adulthood will accelerate the onset or progression of one or more of aging markers, with focus on inflammation, stem cell dysfunction, and cellular senescence. If a life history of injury stress accelerates aging, then we predict that injury survivors will also have shortened lifespans relative to uninjured controls (Aim 1A). Moreover, we will test if a dietary intervention known to delay aging of male African killifish will delay injury-induced accelerated aging and extend the lifespan of injury survivors (Aim 1B). Next, to define the pathways driving injury-induced accelerated aging, we will use multiomics single nuclei RNA and ATAC seq analyses comparing aged injury survivors and uninjured aged controls to identify candidate molecular mechanisms (Aim 2A). We predict that loss of these injury-induced pathways should blunt or diminish injury-induced accelerated aging. We will then use genetic manipulations of identified gene candidates to functionally test their role in stress-induced accelerated aging and shortened lifespan (Aim 2B). R21 funding is essential to establish African killifish in our labs and do this work. Taken together, the proposed studies using a genetically tractable model organism constitutes a rapid experimental pipeline for the identification of gene candidates linking a life history of stress with accelerated aging, candidates that can then be tested in mammals. Thus, these results will open the door to the future creation of therapeutic interventions that will blunt the effect of a life history of stress on aging.


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: 2026 ( Subtotal = $467,181 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	000	1	8/21/2026	NEW	$467,181
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	630 W 168TH ST FL 4	NEW YORK	NY	10032	NEW YORK	USA	Aging Research	001	1	9/3/2026	NEW	$0
														Subtotal = $467,181

Grand Total All Awards = $467,181

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The Scars of Stress: Injury and Aging of African Killifish

Award Number: R21AG104695

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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