# Developing Effective Approaches to Extend Hematopoietic Healthspan by Targeting Cell-extrinsic and Cell-intrinsic Alterations at Middle Age

> **NIH NIH R01** · JACKSON LABORATORY · 2021 · $477,513

## Abstract

PROJECT SUMMARY/ABSTRACT 
 
The process of aging causes functional decline of the hematopoietic system, including reduced capacity for 
regeneration, increased risk of infections, and increased risk of certain forms of blood cancer. This is a 
significant health concern due to the increasing age of our population and incidence of these age-­related 
conditions. No intervention therapies currently exist to extend hematopoietic healthspan with aging, largely due 
to a lack of understanding of the cellular and molecular alterations that cause functional hematopoietic decline. 
Our novel approach is to identify cellular and molecular signatures of functional hematopoietic decline at its 
age of onset, with the rationale that these signatures will point to early causes of decline and hence identify 
prime targets for extending hematopoietic healthspan. Our preliminary data demonstrate that functional 
hematopoietic decline occurs by middle age, that alterations in the bone marrow microenvironment at middle 
age are necessary and sufficient to cause functional hematopoietic decline, and identify alterations in the 
Insulin-­like Growth Factor 1 (IGF1) signaling pathway at middle age as a strong candidate driver of functional 
hematopoietic decline. This project will use cellular and molecular biological approaches in aging mice to 
characterize the hematopoietic cell-­extrinsic and cell-­intrinsic alterations in IGF signaling at middle age that 
cause functional hematopoietic decline. Results of this project will identify targeted, molecular-­ and cell type-­
specific therapeutic strategies to preserve regenerative capacity and immune cell function during aging.

## Key facts

- **NIH application ID:** 10192711
- **Project number:** 5R01DK118072-04
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Jennifer Jean Trowbridge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $477,513
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192711

## Citation

> US National Institutes of Health, RePORTER application 10192711, Developing Effective Approaches to Extend Hematopoietic Healthspan by Targeting Cell-extrinsic and Cell-intrinsic Alterations at Middle Age (5R01DK118072-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10192711. Licensed CC0.

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