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Dietary Restriction, GH/IGF-1 & Mechanisms of Cellular Protection and Regeneration

Award Number: P01AG055369
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2024

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Dietary Restriction, GH/IGF-1 & Mechanisms of Cellular Protection and Regeneration - PROJECT SUMMARY/ABSTRACT TITLE: Dietary Restriction, GH/IGF-1 and Mechanisms of Cellular Protection and Regeneration ABSTACT: Age is the major risk factor for many morbidities including cancer, cardiovascular and neurodegenerative diseases. Biogerontology research is well positioned to help prevent or at least delay these diseases by identifying safe strategies to retard aging so that the degree and type of cellular damage does not reach the threshold leading to disease incidence or progression. Here we propose to bring together two biogerontology laboratories from the University of Southern California School of Gerontology and a laboratory from Harvard University to study the molecular mechanisms linking fasting, fasting mimicking diets and protein restriction to reduced nutrient signaling, the stress resistance signaling network, the mitochondrial peptide humanin, and in turn, cellular protection, regeneration, and healthspan. These studies will contribute to the identification of drugs and dietary interventions to treat as well as prevent multiple diseases by acting on the aging process and on multi-system regeneration and rejuvenation. An important advantage of the dietary interventions being tested is that they are periodic and therefore have the potential to match and possibly surpass the beneficial effects of chronic calorie restriction while minimizing the burden of chronic and extreme diets, but also minimizing adverse effects. This P01 application consists of 3 major projects, an Animal and Biostatistics Core, and an Administrative Core. Our common goals are to: 1) identify and study novel periodic dietary interventions that promote healthspan without causing adverse effects at old ages; 2) study the mechanisms of fasting mimicking diet- and protein restriction-dependent cellular protection, regeneration and rejuvenation with focus on the hematopoietic and nervous systems; 3) understand the link between dietary interventions, growth pathways and humanin to test the hypothesis that this mitochondrial peptide functions as a healthspan mediator and determine whether it can serve as a fasting/protein restriction mimetic; 4) test the hypothesis that endogenous H2S is a key mediator of the protective effects of dietary interventions including fasting, fasting mimicking diets and protein restriction on resistance to ischemic and genotoxic injury to organs and cells, and study the regulation of cysteine gamma lyase-mediated endogenous H2S production by dietary restriction, growth factors and humanin. The unique background of each PI and the close collaboration between them has generated and will continue to generate new hypotheses, novel cellular and mouse models, as well as technical and conceptual developments. These advances will undoubtedly accelerate the research progress and support the development of clinical trials to improve human health in ways that could not be achieved by each laboratory performing research independently.


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 = $0 )
2024	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Aging Research	000	5	4/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $669,874 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Aging Research	000	5	8/7/2023	SUPPLEMENT FOR EXPANSION	$669,874
														Subtotal = $669,874

Issue Date FY: 2022 ( Subtotal = $1,985,236 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	000	5	4/19/2022	NON-COMPETING CONTINUATION	$1,985,236
														Subtotal = $1,985,236

Issue Date FY: 2021 ( Subtotal = $2,402,117 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	002	4	3/26/2021	NON-COMPETING CONTINUATION	$0
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	003	4	3/29/2021	SUPPLEMENT FOR EXPANSION	$411,131
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	001	4	3/18/2021	NON-COMPETING CONTINUATION	$1,990,986
2021	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	000	3	3/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,402,117

Issue Date FY: 2020 ( Subtotal = $2,444,053 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	000	3	2/14/2020	NON-COMPETING CONTINUATION	$2,031,992
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	001	3	7/31/2020	SUPPLEMENT FOR EXPANSION	$412,061
														Subtotal = $2,444,053

Issue Date FY: 2019 ( Subtotal = $2,027,936 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	000	2	1/29/2019	NON-COMPETING CONTINUATION	$2,027,936
														Subtotal = $2,027,936

Issue Date FY: 2018 ( Subtotal = $2,857,734 )
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	003	1	9/6/2018	SUPPLEMENT FOR EXPANSION	$412,475
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER STREET THIRD FLOOR	LOS ANGELES	CA	90089	LOS ANGELES	USA	Aging Research	000	1	2/13/2018	NEW	$1,916,594
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	002	1	9/5/2018	SUPPLEMENT FOR EXPANSION	$403,105
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Aging Research	001	1	8/31/2018	NEW	$125,560
														Subtotal = $2,857,734

Grand Total All Awards = $12,386,950

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Dietary Restriction, GH/IGF-1 & Mechanisms of Cellular Protection and Regeneration

Award Number: P01AG055369

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2024

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