# Project 2: Thymic and peripheral Aspects of T cell Aging and Rejuvenation

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2020 · $382,864

## Abstract

PROJECT 2: RESPONSE OF THE AGED THYMUS TO INJURY AND REJUVENATION
ABSTRACT
Even though the thymus is is exquisitely sensitive to acute injury such as that caused by infection, shock, or
common cancer therapies such as cytoreductive chemo- or radiation therapy, it also has a remarkable capacity
for endogenous repair. However, this capacity declines with age and is a major clinical hurdle in elderly
patients who receive an immune insult such as that caused by common cancer cytoreductive therapies and the
conditioning required for hematopoietic stem cell transplantation (HSCT).
The premise of this project is that the thymic regenerative response to acute injury is weakened with
age and correlates with age-related thymic involution. We will compare and contrast what we know about
the cellular and molecular pathways that underpin thymic regeneration in young animals, to the regenerative
response in mice during normal thymic aging; and develop rational intervention strategies to improve
regeneration in aged mice. In this project, we will comprehensively assess the endogenous regenerative
response over lifespan (SA1), perform studies to better understand the underlying mechanisms governing
endogenous thymic regeneration and their breakdown in aged mice (SA2), and test known and putative
strategies to determine their effectiveness in promoting thymopoiesis in aged tissue that has undergone
damage (SA3).
Our project has multiple points of interaction with the other projects and cores of this P01, including providing
the basis for exploring the role of endothelial cells (ECs) and BMP4 in thymic and SLO aging. Together, these
aims support the overarching goal of the P01 to identify the mechanisms responsible for defects in thymic
production of naïve T cells with age. The mechanistic and pre-clinical studies outlined have the potential to
define important novel pathways underlying thymic regeneration, which could result in clinical approaches to
enhance T cell immunity in patients whose thymus has been decimated due to age-related involution.

## Key facts

- **NIH application ID:** 9967950
- **Project number:** 5P01AG052359-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Marcel R M van den Brink
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,864
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9967950

## Citation

> US National Institutes of Health, RePORTER application 9967950, Project 2: Thymic and peripheral Aspects of T cell Aging and Rejuvenation (5P01AG052359-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9967950. Licensed CC0.

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