Tuesday, November 18, 2025 11/18/2025

Molecular mechanisms of cellular response to age-associated chromatin changes

Award Number: R01AG081347
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Molecular mechanisms of cellular response to age-associated chromatin changes - PROJECT SUMMARY Profound changes in chromatin occur in aged cells and tissues. These changes, such as altered histone modifications and chromatin conformation, lead to loss of heterochromatin, reduced nucleosome stability, and aberrant transcription, all of which have been causally linked to the aging process. Using yeast strains with reduced histone dosage, a model mimicking the situation of aged cells, we uncovered a cellular response to such chromatin defects, named chromatin architectural defects (CAD) response or simply chromatin stress response. Like cellular stress to heat and oxidation where moderate levels of stress can lead to hormesis, a beneficial effect, activating CAD response with moderate chromatin defects extends lifespan, offering a new intervention strategy to antagonize aging and age-related diseases. However, many mechanistic details of this response remain unexplored. This project will focus on these mechanistic questions. Does the CAD response directly mitigate age-associated chromatin changes and defects, such as disrupted heterochromatin, loss of transcription silencing and cryptic transcription? TOR inhibition is critical for the longevity effect of CAD response. How does the CAD response crosstalk with other TOR-related stress response pathways? In particular, does the CAD response interact with Isw2-regulated longevity-promoting stress responses? How does CAD response interact with metabolic changes? What are the regulators and effectors of CAD response? Importantly, how does the previously identified CAD response transcription factor Gis1 function to activate the transcriptional response? Addressing these questions pertaining to detailed molecular mechanisms will help characterize CAD response with molecular regulators and effectors, physiological effects to the cell, and relationships with other stress response and metabolic pathways. These mechanistic details will establish CAD response as a novel form of stress response with hormetic effects that promote longevity.


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: 2025 ( Subtotal = $329,280 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Aging Research	000	3	3/7/2025	NON-COMPETING CONTINUATION	$302,400
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Aging Research	001	3	6/9/2025	NON-COMPETING CONTINUATION	$26,880
														Subtotal = $329,280

Issue Date FY: 2024 ( Subtotal = $336,000 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Aging Research	000	2	4/18/2024	NON-COMPETING CONTINUATION	$336,000
														Subtotal = $336,000

Issue Date FY: 2023 ( Subtotal = $336,000 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Aging Research	000	1	3/28/2023	NEW	$336,000
														Subtotal = $336,000

Grand Total All Awards = $1,001,280

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Molecular mechanisms of cellular response to age-associated chromatin changes

Award Number: R01AG081347

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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