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Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies

Award Number: UH3AG064704
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2019
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies - PROJECT ABSTRACT. Centenarians (ages >100 yrs) and even more-so, semi-supercentenarians (ages 105-109 yrs) and supercentenarians (110+ yrs) are outliers not only for their exceptionally long lifespans, but also for their longer female fertility and resistance to aging-related disability and morbidities such as Alzheimer’s disease, heart disease, stroke, diabetes and cancer. Their offspring also exhibit delayed morbidity and lower mortality compared to their birth cohort. Among non-human species, rodents including the naked mole rat have also gained attention for their variation in lifespan compared to other mammals with similar body mass. Proteomic signatures associated with extreme longevity (EL) in centenarians and integrated transcriptomic and proteomic data in NMRs suggest that integrated analyses of multiple omics data generated from these human and animal models of slow aging and resistance to aging related diseases can inform us about biological mechanisms that underlie these survival and health advantages and, ultimately, about potential therapeutics to prevent diseases such as Alzheimer’s. Two specific aims parallel the UH2 and UH3 phases of this proposal. Aim 1: In the UH2 phase, the New England Centenarian Study and the Einstein Centenarian and Offspring studies will establish a standardized phenotypic data and biological sample collection protocol for in-person visits of 700 subjects from each study (n=1400). Detailed cognitive function testing will determine presence or absence of probable Alzheimer’s. The phenotyping protocol will be the same as that used by the Longevity Consortium’s Centenarian Project (n=350), so that their data can be added to this effort for a total sample of 1,750. A world-class multidisciplinary team will plan the multi-omics data generation and analytic and translation efforts to be executed in Aim 2. These efforts will be paralleled by comparative transcriptomic, proteomic and microbiomic studies of non-human mammalian species of widely different life spans and by the creation of a library of EL-specific IPSCs that will be differentiated into unlimited numbers of hepatocytes and neurons. Aim 2: In the UH3 phase, we will generate transcriptomic, methylomics, metabolomics, proteomic and microbiomic data from centenarians and centenarian offspring (generated from two time points in about a third of the sample). Methods for multi-omic data integration compiled in Aim 1 will be used to discover molecular profiles that associate with EL and healthy aging phenotypes including delay of or escape from Alzheimer’s disease. Integration with molecular profiles from functional studies of resiliency performed with iPSC-derived neurons and hepatocytes and with molecular profiles associated with increased lifespan from multiple species will point to mechanisms and generate candidate small molecule and compound therapeutics. All generated data and unique biological resources, including the EL- iPSC derived hepatocytes and neurons, will be shared with consortia and individual investigators researching Alzheimer’s, other aging related diseases and more generally, basic mechanisms of 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 = $0 )
2026	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	5	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $4,752,126 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	5	2/14/2025	NON-COMPETING CONTINUATION	$4,364,197
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	001	5	7/22/2025	NON-COMPETING CONTINUATION	$387,929
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	002	5	8/8/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $4,752,126

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	001	4	8/1/2024	NON-COMPETING CONTINUATION	$0
2024	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	4	3/19/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $6,586,224 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	002	4	8/2/2023	NON-COMPETING CONTINUATION	$4,939,661
2023	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	001	3	6/29/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
2023	2022	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	3	6/23/2023	EXTENSION WITH OR WITHOUT FUNDS	$1,646,563
														Subtotal = $6,586,224

Issue Date FY: 2022 ( Subtotal = $4,998,007 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Aging Research	000	3	8/26/2022	EXTENSION WITH OR WITHOUT FUNDS	$4,998,007
														Subtotal = $4,998,007

Grand Total All Awards = $16,336,357

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Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies

Award Number: UH3AG064704

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/15/2019

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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