# Identifying A Skeleton-Derived Factor for Vascular Aging

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $491,248

## Abstract

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.

## Key facts

- **NIH application ID:** 10202909
- **Project number:** 1R01AG072090-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Mei Wan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $491,248
- **Award type:** 1
- **Project period:** 2021-04-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202909

## Citation

> US National Institutes of Health, RePORTER application 10202909, Identifying A Skeleton-Derived Factor for Vascular Aging (1R01AG072090-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10202909. Licensed CC0.

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