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Molecular mechanisms underlying the preservation of neural stem cell quiescence during aging

Award Number: R01AG053268
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Molecular mechanisms underlying the preservation of neural stem cell quiescence during aging - PROJECT SUMMARY – ORIGINAL APPLICATION Cognitive decline is a major feature of aging and neurodegenerative diseases such as Alzheimer’s disease. Neurogenesis, the formation of new neurons, supports learning, memory, mood regulation, and sensory functions in the healthy mammalian brain. During aging, neurogenesis is dramatically reduced due to impairments in neural stem cell (NSC) pools. The mechanisms responsible for dysfunction of the NSC reservoir are not fully understood, but significant evidence implicates changes to the quiescent NSCs, which are the source of the neurogenic lineage. This work investigates the mechanisms responsible for failed activation of quiescent NSCs with age. This project is significant because identification of the mechanisms underlying dysfunction of quiescent NSCs with age will reveal strategies to restore new neuron formation in aging and neurodegeneration. Published and preliminary work shows that quiescent NSCs, though relatively dormant, are defective at the chromatin, gene expression, and metabolic levels with age. This study takes an integrated approach to reveal the specific target genes and processes responsible for defects in NSC quiescence with age. Specific Aim 1 will investigate how mitophagy regulates metabolic health of NSCs during aging. Aim 2 employs an integrated multi- omics strategy to fully elucidate the epigenomic and metabolic changes that occur the neurogenic lineage with age. Finally, Aim 3 will address the mechanisms by which NSCs return to quiescence, and the extent to which failure in this process results in depletion of the functional NSC pool with age. Collectively, this work will result in a comprehensive understanding of how dormant NSCs are affected by aging in the mammalian brain. In the long term, these studies have the potential to lead to the development of interventions to improve healthy aging and restore cognition in the context of neurodegeneration.


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 = $572,715 )
2025	2025	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	000	8	7/29/2025	EXTENSION WITH OR WITHOUT FUNDS	$572,715
														Subtotal = $572,715

Issue Date FY: 2023 ( Subtotal = -$618,203 )
2023	2021	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	001	5	7/25/2023	SUPPLEMENT FOR EXPANSION	-$336,256
2023	2021	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	5	7/25/2023	NON-COMPETING CONTINUATION	-$281,947
														Subtotal = -$618,203

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	001	5	8/8/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2021	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	5	8/8/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $730,416 )
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	5	4/5/2021	NON-COMPETING CONTINUATION	$333,125
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	001	5	4/19/2021	SUPPLEMENT FOR EXPANSION	$397,291
														Subtotal = $730,416

Issue Date FY: 2020 ( Subtotal = $333,125 )
2020	2020	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	4	4/6/2020	NON-COMPETING CONTINUATION	$333,125
														Subtotal = $333,125

Issue Date FY: 2019 ( Subtotal = $816,402 )
2019	2019	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	001	3	6/6/2019	SUPPLEMENT FOR EXPANSION	$406,250
2019	2019	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	3	4/1/2019	NON-COMPETING CONTINUATION	$410,152
														Subtotal = $816,402

Issue Date FY: 2018 ( Subtotal = $407,261 )
2018	2018	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	2	4/30/2018	NON-COMPETING CONTINUATION	$407,261
														Subtotal = $407,261

Issue Date FY: 2017 ( Subtotal = $379,913 )
2017	2017	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	001	1	9/13/2017	SUPPLEMENT FOR EXPANSION	$46,788
2017	2017	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	1	3/28/2017	NEW	$333,125
														Subtotal = $379,913

Grand Total All Awards = $2,621,629

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Molecular mechanisms underlying the preservation of neural stem cell quiescence during aging

Award Number: R01AG053268

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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