Monday, June 30, 2025 6/30/2025

Age-related vascular cognitive impairment: role of endothelial senescence

Award Number: R01AG068295
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: 07/31/2025

Group Awards By:

View Award Description

Age-related vascular cognitive impairment: role of endothelial senescence - PROJECT SUMMARY/ ABSTRACT More than 50 million people over the age of 65 are currently affected by vascular cognitive impairment and dementia (VCID). Although the specific mechanisms for aging- induced VCID are not yet known, there is increasing evidence that alterations of the neurovascular unit play a crucial role. The objective of this proposal is to elucidate the mechanistic role of senescence-related endothelial dysfunction in cognitive impairment. The central hypothesis is that aging primarily promotes endothelial senescence in the brain and subsequent dysfunction, altering the production of vasodilator mediators, impairing neurovascular coupling responses, promoting blood-brain barrier (BBB) disruption and microvascular rarefaction. The resulting decline in cerebral blood flow (CBF) and increased neuroinflammation contribute to cognitive impairment. The proposed work is novel as it will be the first to demonstrate that aging-induced endothelial senescence is a critical contributing factor to the pathogenesis of VCID. The results will likely identify specific mechanisms and reveal potential therapies that are capable of improving CBF and restoring learning and memory. The following aims are proposed: 1) Determine how endothelial senescence alters neurovascular coupling responses, CBF and cognition in aging. The working hypothesis is that aging-induced activation of p16-dependent cellular senescence program in endothelial cells impairs vasodilator function. It is predicted that elimination of senescent endothelial cells, through genetic manipulation or through senolytic therapies will restore neurovascular function and improve CBF and cognition in aged mice. 2) Determine how senescence alters microvascular density and BBB integrity in aging. The working hypothesis is that activation of p16-dependent cellular senescence program in endothelial cells impairs endothelial barrier function and compromise the maintenance of the microcirculatory network. It is predicted that elimination of senescent cells will restore BBB, attenuating neuroinflammation and increase cerebromicrovascular density in aged mice. 3) Determine cellular heterogeneity among senescent endothelial cells in conjunction with their morphological and functional characteristics. Together, the proposed studies will identify a fundamental mechanism governing aging-induced cerebrovascular changes eventually leading to cognitive impairment.


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 = $362,500 )
2024	2024	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Aging Research	000	5	7/23/2024	NON-COMPETING CONTINUATION	$362,500
														Subtotal = $362,500

Issue Date FY: 2023 ( Subtotal = $362,500 )
2023	2023	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Aging Research	000	4	8/23/2023	NON-COMPETING CONTINUATION	$362,500
2023	2023	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Aging Research	001	4	9/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $362,500

Issue Date FY: 2022 ( Subtotal = $362,500 )
2022	2022	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Aging Research	000	3	7/26/2022	NON-COMPETING CONTINUATION	$362,500
														Subtotal = $362,500

Issue Date FY: 2021 ( Subtotal = $362,500 )
2021	2021	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Aging Research	000	2	7/19/2021	NON-COMPETING CONTINUATION	$362,500
														Subtotal = $362,500

Issue Date FY: 2020 ( Subtotal = $362,500 )
2020	2020	UNIVERSITY OF OKLAHOMA	865 RESEARCH PKWY STE 530	OKLAHOMA CITY	OK	73104	OKLAHOMA	USA	Aging Research	000	1	7/23/2020	NEW	$362,500
														Subtotal = $362,500

Grand Total All Awards = $1,812,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Age-related vascular cognitive impairment: role of endothelial senescence

Award Number: R01AG068295

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: 07/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer