# Uncovering the role of macrophage/vascular crosstalk in tissue aging

> **NIH NIH F32** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $20,577

## Abstract

Billions of cells die every day in our bodies as a result of normal tissue turnover and environmental stress.
Macrophages are an immune cell population that play a critical role in clearing this cellular debris and promoting
tissue repair. Macrophages reside in distinct sub-tissue locations or niches, such as blood vessels or nerves,
and are thought to support specialized tissue functions. There is a mounting evidence of a link between reduced
blood vessel function and many age-associated diseases including diabetes, atherosclerosis, chronic obstructive
pulmonary disease (COPD) and neurodegenerative conditions, such as Alzheimer’s disease. Similarly,
macrophages show impaired phagocytic capacity in tissues with age-associated pathologies. However, the
functional interplay between macrophages and blood vessels as well as how this crosstalk potentially breaks
down during tissue aging remains unclear. Therefore, I aim to identify: 1) molecular signals that facilitate
macrophage/vascular crosstalk, 2) the relative role of systemic and local factors in promoting aging of
the vascular niche as well as 3) the molecular alterations that drive macrophage decline and vascular
aging. Conventional methods have provided limited insights, due mainly to our inability to capture the spatial
and temporal dynamics of this process under physiological conditions, such as in living animals. Therefore, I
have set up intravital imaging approaches to visualize and manipulate macrophages and blood vessels in the
skin of living mice. 1) First, by utilizing intravital microscopy, I will opto-genetically label and isolate cells from the
skin vascular niche for single cell RNA-sequencing to identify signaling pathways with active ligand/receptor pair
expression. From this, I will use a novel light-inducible Cre-recombinase to functionally interrogate the role of
these signaling pathways in spatiotemporally-defined regions of the skin vasculature to track direct changes to
macrophage behavior and vascular function. 2) Secondly, by performing intravital time-lapse imaging in both
young and old mice, I will identify which cellular behaviors are altered in the vascular niche with age, including
macrophage phagocytosis, vascular density, blood flow and vascular debris accumulation. Furthermore, I will
perform heterochronic parabiosis to determine the relative role of the systemic milieu in modulating these
functional changes in the vascular niche. 3) Finally, I will isolate cells from the vascular niche of young, middle-
aged, and old mice and perform single cell RNA-sequencing to identify differential gene expression patterns of
the vascular niche during aging. I will then use cell type-specific inducible Cre-recombinases to knock out genes
in these pathways to test their potential roles in vascular aging. To date, the cellular and molecular mechanisms
that alter macrophage and vascular function with age remain unknown. Work from this proposal will provide a
basic understanding ...

## Key facts

- **NIH application ID:** 10156723
- **Project number:** 1F32AG071336-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Kailin Riley Mesa
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $20,577
- **Award type:** 1
- **Project period:** 2021-04-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156723

## Citation

> US National Institutes of Health, RePORTER application 10156723, Uncovering the role of macrophage/vascular crosstalk in tissue aging (1F32AG071336-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10156723. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*