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Spatial Mapping Senescent Cells Across the Mouse Lifespan by Multiplex Transcriptomics and Epigenomics

Award Number: U54AG079758
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Spatial Mapping Senescent Cells Across the Mouse Lifespan by Multiplex Transcriptomics and Epigenomics - PROJECT SUMMARY Cellular senescence, characterized by stable proliferation arrest and secretion of pro-inflammatory factors, is not only a hallmark of aging, but also a key contributor to age-associated diseases in humans. As the US population is aging, there is an added urgency to gain a better understanding of cellular senescence in different tissues over the lifespan. Unfortunately, we still lack the knowledge to unambiguously define senescence at the molecular and cellular levels, due to its heterogeneous phenotypes. To address this major gap in knowledge, we propose to establish a tissue mapping center that focuses on the identification and characterization of senescent cells in healthy mouse brain, bone marrow, breast, colon and liver. Our research strategy builds on recent advances in single cell epigenomics technologies that our team developed and the knowledge that senescent cells exhibit characteristic changes in the chromatin landscapes and histone modifications along with gene expression levels at marker genes of cellular senescence. We will deploy cutting-edge single cell in situ and tissue dissociative multi-omic tools that have been well established in our center to produce comprehensive single cell resolution maps of the transcriptome and epigenome in male and female mouse brain, bone marrow, breast, colon and liver, and to provide qualitative and quantitative spatial maps of the normal burden of senescent cells in these vital organs, across the lifespan of two mouse strains. We will rigorously validate the newly defined senescent cell populations using pharmacologic and genetic approaches to eradicate senescent cells or suppress their inflammatory phenotype, and orthogonal state-of-the-art and conventional assays for cellular senescence. We will generate whole genome single cell DNA methylation data to link our spatial atlas to measurement of epigenetic age, a candidate predictor of beneficial versus detrimental effects of senescent cells. We expect that comprehensive single cell atlases of epigenome and transcriptome will enable us to identify and characterize cellular senescence in different tissue contexts and during aging. We expect that the planned research will provide a reference for future studies that seek to characterize and target senescent cells associated with or preceding disease in brain, bone marrow, breast, colon and liver.


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 = $2,889,150 )
2025	2025	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	002	4	8/19/2025	SUPPLEMENT FOR EXPANSION	$198,900
2025	2025	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	001	4	8/5/2025	NON-COMPETING CONTINUATION	$2,690,250
2025	2024	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	3	2/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,889,150

Issue Date FY: 2024 ( Subtotal = $2,690,250 )
2024	2024	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	001	3	7/8/2024	NON-COMPETING CONTINUATION	$2,690,250
2024	2023	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	2	2/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,690,250

Issue Date FY: 2023 ( Subtotal = $2,690,250 )
2023	2023	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	001	2	7/17/2023	NON-COMPETING CONTINUATION	$2,690,250
2023	2022	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	1	2/7/2023	NEW	$0
														Subtotal = $2,690,250

Issue Date FY: 2022 ( Subtotal = $2,566,784 )
2022	2022	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Trans-NIH Research Support	000	1	7/28/2022	NEW	$2,566,784
														Subtotal = $2,566,784

Grand Total All Awards = $10,836,434

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Spatial Mapping Senescent Cells Across the Mouse Lifespan by Multiplex Transcriptomics and Epigenomics

Award Number: U54AG079758

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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