Wednesday, July 2, 2025 7/2/2025

Identifying A Skeleton-Derived Factor for Vascular Aging

Award Number: R01AG072090
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2025

Group Awards By:

View Award Description

Identifying A Skeleton-Derived Factor for Vascular Aging - ABSTRACT/SUMMARY Cardiovascular and cerebrovascular diseases are the leading causes of mortality and disability, especially in the elderly population. Accumulating evidence suggest that circulating pro-aging factors derived from distal organs exacerbate the aging of vascular system. Particularly, there is a link between bone metabolism and the vasculature. Clinical studies have shown an inverse, independent correlation between osteoporosis and vascular events, such as aortic stiffening and cerebrovascular disease. Therefore, the bone-vascular interplay likely involves mechanisms underlying the aging of cardiovascular and cerebrovascular system. Our goal is to identify skeleton-derived factors that accelerate vascular aging through blood circulation. We recently found that old animals have elevated serum level of angiogenesis factor PDGF-BB and develop increased aortic stiffness and reduced density and integrity of brain capillaries relative to young mice. Importantly, acute infusion of aged plasma into young mice induces an elevation in serum PDGF-BB concentration and a similar cerebrovascular phenotype as seen in aged mice. We previously found that pre-osteoclasts (Pre-OCs) in bone/bone marrow is a major cell type that secret PDGF-BB. Our preliminary data show that Pre-OCs undergo cellular senescence and secrete high amount of PDGF-BB during aging. Our results suggest that Pre-OCs in bone/bone marrow is a main source of elevated circulating PDGF-BB during aging. While PDGF-BB maintains the homeostasis of vasculature under physiological conditions, abnormally high concentration of PDGF-BB may lead to vascular impairment. Our central hypothesis is that skeleton-derived PDGF-BB is a systemic pro-aging factor to exacerbate arterial stiffening and cerebrovascular dysfunction. In Aim 1, we will establish the role of PDGF-BB as a systemic factor to exacerbate vascular aging by conducting plasma transfer and heterochonic parabiosis studies to examine whether young mice develop age-associated aortic and cerebrovascular phenotype by exposure to the blood of aged mice or Pdgfb transgenic mice. In Aim 2, we will define the contribution of senescent Pre-OCs to vascular aging by conducting bone marrow transplantation experiments. We will also test if ablation of Pre-OCs or inhibition of the senescence of Pre-OCs rescues the aortic and cerebrovascular pathologies in aged mice. Positive findings will uncover the mechanisms by which skeletal cells regulate vascular aging and will provide an unconventional but promising path for the treatment of cardiovascular and cerebrovascular diseases.


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 = $411,442 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	000	5	12/16/2024	NON-COMPETING CONTINUATION	$411,442
														Subtotal = $411,442

Issue Date FY: 2024 ( Subtotal = $466,164 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	001	4	5/22/2024	NON-COMPETING CONTINUATION	$46,617
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	000	4	12/29/2023	NON-COMPETING CONTINUATION	$419,547
														Subtotal = $466,164

Issue Date FY: 2023 ( Subtotal = $477,389 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	000	3	1/20/2023	NON-COMPETING CONTINUATION	$477,389
														Subtotal = $477,389

Issue Date FY: 2022 ( Subtotal = $485,943 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	001	2	4/26/2022	NON-COMPETING CONTINUATION	$48,595
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	000	2	12/30/2021	NON-COMPETING CONTINUATION	$437,348
														Subtotal = $485,943

Issue Date FY: 2021 ( Subtotal = $491,248 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Aging Research	000	1	3/31/2021	NEW	$491,248
														Subtotal = $491,248

Grand Total All Awards = $2,332,186

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Identifying A Skeleton-Derived Factor for Vascular Aging

Award Number: R01AG072090

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer