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Defining Strategies to Target Energy Failure in Metabolically Vulnerable Human Cells

Award Number: R01AG065428
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Defining Strategies to Target Energy Failure in Metabolically Vulnerable Human Cells - Project Summary Disrupted energy metabolism is a central driver of dysfunction and death in a wide range of diseases, and may also contribute to aging. Energy failure, or insufficient energy to support normal function, can lead to neurodegenerative diseases, ischemia and heart failure, while an imbalance in energy production may contribute to cancer. As such, boosting energy levels has great therapeutic potential to improve cellular function and survival. However, there are only anecdotal examples of how to increase or preserve cellular ATP levels. To address this critical unmet need for anti-aging and energy-focused therapeutics, we developed an innovative high throughput screen that uses a fluorescent biosensor to measure ATP levels in individual cells, and used it to identify genes and pathways that regulate ATP levels. In this proposal, we will test our central hypothesis that increasing ATP can enhance the function and survival of vulnerable cells, but the efficacy depends on the mechanism by which ATP is increased. The overall objectives of our proposed study are to define the most robust mechanisms to increase cellular energy levels, and to determine if increasing ATP boosts the function and survival of human cells that are susceptible to diseases of energy failure. We will accomplish these objectives in two specific aims. (1) We will use metabolomics, transcriptomics and assays of energy production and consumption to determine the broad mechanisms by which energy levels can be increased. (2) We will determine if increasing the ATP level can enhance the function and survival of human neurons and cardiomyocytes. Overall, these studies will i) determine the broad cellular mechanisms by which cellular energy levels can be increased, and ii) begin to assess the therapeutic potential of increasing energy levels to protect against energy failure in metabolically vulnerable human cells.


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: 2024 ( Subtotal = $620,722 )
2024	2024	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Aging Research	000	5	4/22/2024	NON-COMPETING CONTINUATION	$620,722
														Subtotal = $620,722

Issue Date FY: 2023 ( Subtotal = $645,796 )
2023	2023	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Aging Research	000	4	5/19/2023	NON-COMPETING CONTINUATION	$645,796
														Subtotal = $645,796

Issue Date FY: 2022 ( Subtotal = $1,106,171 )
2022	2022	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Aging Research	004	3	6/13/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2022	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Aging Research	003	3	6/2/2022	SUPPLEMENT FOR EXPANSION	$460,375
2022	2022	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Aging Research	002	3	5/16/2022	NON-COMPETING CONTINUATION	$645,796
2022	2021	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Aging Research	000	2	11/3/2021	NON-COMPETING CONTINUATION	$0
2022	2021	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Aging Research	001	2	11/17/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,106,171

Issue Date FY: 2021 ( Subtotal = $645,796 )
2021	2021	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Aging Research	000	2	6/3/2021	NON-COMPETING CONTINUATION	$645,796
														Subtotal = $645,796

Issue Date FY: 2020 ( Subtotal = $690,296 )
2020	2020	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Aging Research	000	1	8/12/2020	NEW	$690,296
														Subtotal = $690,296

Grand Total All Awards = $3,708,781

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Defining Strategies to Target Energy Failure in Metabolically Vulnerable Human Cells

Award Number: R01AG065428

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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