# Senescence in the Foreign Body Response Across Lifespan

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $660,510

## Abstract

The overall goal of this proposal is to characterize senescent cells (SnCs) and their communication networks
during fibrosis induced by the foreign body response (FBR), specifically with respect to biomaterials, across the
lifespan. SnCs are rare but impactful cells that contribute to multiple biological processes; to date, their identity
and function in vivo, including interactions with the immune system, remain elusive. We recently discovered
that SnCs contribute to fibrosis induced by the FBR in young animals. In preliminary studies, we found
senescent pericytes and fibroblasts in the FBR that each had a unique senescence-associated secretory
phenotype (SASP) and that communicated with different macrophage subpopulations. We also found
differences in SnC induction and phenotype in older animals, and sex differences in the immune response to
implants in both young and aged mice. In older animals, for example, SnC communication shifted toward
increased communication with T cells. We developed an approach that defines senescence signatures
(SenSigs) from transgenic p16-Cre reporter mice that can be used in combination with transfer learning
methods to predict which cells are senescent in single-cell datasets. Using these transgenic tools and
computational approaches, the proposed research will address long -standing questions of SnC phenotype,
heterogeneity, function, and immunological interactions in the context of fibrosis in the foreign body response.
We anticipate that this will enable development of more sophisticated and targeted senolytic therapies for the
FBR and for fibrosis in general. Our Aims are:
Specific Aim 1. Define senescent cell types and their senescence signature in the FBR across lifespan in
male and female p16-reporter mice.
Specific Aim 2. Define SnCs and their communication patterns in the FBR.
Specific Aim 3. Determine the functional role of SnCs and SnC-subtypes on immune response and tissue
structure.

## Key facts

- **NIH application ID:** 10882147
- **Project number:** 1R01AG082965-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** JENNIFER H ELISSEEFF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $660,510
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882147

## Citation

> US National Institutes of Health, RePORTER application 10882147, Senescence in the Foreign Body Response Across Lifespan (1R01AG082965-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10882147. Licensed CC0.

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