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Targeting Cellular Senescence to Extend Healthspan

Award Number: P01AG062413
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2019
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Targeting Cellular Senescence to Extend Healthspan - OVERALL: Targeting Cellular Senescence to Extend Healthspan – SUMMARY This proposal is for the renewal of P01 AG62413, Targeting Cellular Senescence to Extend Healthspan. In the initial funding cycle, we made major conceptual and technical advances in the understanding of cellular senescence, its mechanistic role in the aging of three distinct tissues, and its modifiability by pharmacological intervention. The influence and impact of this highly collaborative PPG are highlighted by over 130 publications, complementary grants, career development awards, and significant engagement in the Common Fund Cellular Senescence Network. Moreover, several clinical trials have been initiated, consistent with the overall goal to build a firm foundation of multidisciplinary discovery science in cellular senescence that leads to a pipeline of therapeutic strategies that slow or prevent age-associated diseases.to drive translational geroscience forward. Our progress has also yielded several exciting and critical questions centered on the molecular underpinnings of the senescence program, including the unique and overlapping roles of p16Ink4a and p21Cip1, the role of specific senescent cell sub-types in tissue and systemic aging, and the tractability of these cell populations by next-generation small molecules engineered to promote their elimination (senolytics) or alter their behavior (senomorphics). We have assembled a uniquely qualified, highly collaborative, and multidisciplinary team to pursue these new and important scientific directions in the renewal through three tissue-centered projects and four highly complementary cores. The projects are Cellular Senescence and Bone Aging (Project 1), Cellular Senescence and Skeletal Muscle Aging (Project 2), and Cellular Senescence and Brain Aging (Project 3). The multidisciplinary cores consist of an Administrative and Systems Biology Core (Core A), a Common Mouse Models Core (Core B), a Drug Discovery and Development Core (Core C), and a Senescence Molecular Phenotyping Core (Core D), each armed with innovative technologies and the appropriate expertise. Collectively, through the coordination, integration, and analysis of research activities and results across the three projects and four cores detailed in this application, this PPG will yield fundamental insights into the governing roles of p16Ink4a and p21Cip1 in cellular senescence and aging, critical data on the therapeutic potential of senotherapeutic compounds for age-related tissue dysfunction, and an advanced understanding and new hypotheses regarding cellular senescence as a mediator of inter-organ communication between bone, skeletal muscle, and brain.


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 = $3,158,891 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	8	1/21/2026	NON-COMPETING CONTINUATION	$3,158,891
														Subtotal = $3,158,891

Issue Date FY: 2025 ( Subtotal = $3,449,656 )
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	002	7	6/18/2025	NON-COMPETING CONTINUATION	$281,603
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	7	3/12/2025	NON-COMPETING CONTINUATION	$3,168,053
2025	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	5	3/27/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,449,656

Issue Date FY: 2024 ( Subtotal = $3,544,455 )
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	6	4/25/2024	COMPETING CONTINUATION	$3,544,455
2024	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	5	4/17/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,544,455

Issue Date FY: 2023 ( Subtotal = $2,819,749 )
2023	2023	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	5	2/1/2023	NON-COMPETING CONTINUATION	$2,819,749
2023	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	4	10/27/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,819,749

Issue Date FY: 2022 ( Subtotal = $2,835,446 )
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	4	2/3/2022	NON-COMPETING CONTINUATION	$2,551,899
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	002	4	5/6/2022	NON-COMPETING CONTINUATION	$283,547
2022	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	3	11/16/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,835,446

Issue Date FY: 2021 ( Subtotal = $2,841,000 )
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	3	7/16/2021	NON-COMPETING CONTINUATION	$0
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	3	2/11/2021	NON-COMPETING CONTINUATION	$2,841,000
														Subtotal = $2,841,000

Issue Date FY: 2020 ( Subtotal = $3,243,964 )
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	002	2	7/31/2020	SUPPLEMENT FOR EXPANSION	$397,500
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	001	2	7/21/2020	NON-COMPETING CONTINUATION	$0
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	2	2/13/2020	NON-COMPETING CONTINUATION	$2,846,464
														Subtotal = $3,243,964

Issue Date FY: 2019 ( Subtotal = $2,897,046 )
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Aging Research	000	1	5/30/2019	NEW	$2,897,046
														Subtotal = $2,897,046

Grand Total All Awards = $24,790,207

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Targeting Cellular Senescence to Extend Healthspan

Award Number: P01AG062413

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2019

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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