# Nutrient Sensing, Hematopoietic Stem Cell Metabolism and Aging

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $392,500

## Abstract

Project Summary
The maintenance of the hematopoietic system throughout adult life relies on the
persistence of hematopoietic stem cells (HSCs). With age, the ability of HSCs to self-
renew declines and the differentiation potential of HSCs is dysregulated. HSC aging is
thought to be a major cause of compromised maintenance of the hematopoietic system
in the aged animals. Understanding the molecular mechanisms underlying HSC aging
holds the promise to identify novel molecular targets to ameliorate age-related
deterioration in HSCs and to prevent bone marrow failure. Calorie restriction (CR), a
dietary regimen known to extend lifespan across species, greatly prevents hematopoietic
senescence, improves HSC function, and suppresses myeloid leukemia development.
We propose to use CR as a platform to search for genetic regulators that modulate HSC
aging and diseases of HSC origin.
We have established a CR mouse model to study the effects of nutrient on HSC aging.
Using the established system, we will elucidate the nutrient sensors and their
downstream signaling events that relay the nutrient signals to maintain mitochondrial
metabolic homeostasis and regulate HSC fate choices. We will also determine how this
process is dysregulated during the aging process. This application is significant because
it addresses outstanding questions of the SHINE program: 1) What are the regulatory
factors governing aged HSC fate choices? 2) Are HSC-intrinsic changes coordinated
with extrinsic signals during aging? 3) How do HSC metabolic processes change with
age? 4) Can these HSC metabolic processes be modified to rejuvenate the blood
system?

## Key facts

- **NIH application ID:** 10219149
- **Project number:** 5R01AG063404-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** DANICA CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219149

## Citation

> US National Institutes of Health, RePORTER application 10219149, Nutrient Sensing, Hematopoietic Stem Cell Metabolism and Aging (5R01AG063404-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10219149. Licensed CC0.

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