# Understanding the aging process in hematopoietic stem cells by alcohol-induced DNA damage

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2024 · $194,453

## Abstract

Project Summary
Alcohol is a common potential source of DNA damage in humans. Indeed, its metabolic byproducts,
acetaldehyde and reactive oxygen species (ROS), mutate hematopoietic stem cells (HSCs). Importantly, DNA
damage is central to the aging process by contributing to stem cell exhaustion, cellular senescence, inflammation,
and deregulated nutrient sensing. Together, these findings have led us to hypothesize that alcohol-induced DNA
damage accelerates aging in HSCs. Moreover, aged HSCs have myeloid-biased differentiation, reduced long-
term repopulating potential and decreased DNA repair function, which may lend themselves to being more
vulnerable to alcohol-induced DNA damage. Prior research has used very high doses of alcohol to study their
DNA-damaging effects on HSCs, which is difficult to generalize to the broader aging population who may enjoy
only moderate alcohol drinking. Also, the effects of moderate alcohol consumption on overall health in the general
population remain controversial. The overarching goal of this proposal is to shed light on the key aspects of HSC
aging using cell-based and animal models. We aim to identify DNA repair genes essential for repairing alcohol-
induced DNA damage in HSCs by a pooled CRISPR screen. We also aim to determine whether aged HSCs are
more vulnerable to moderate alcohol drinking using a mouse bone marrow transplant model and a single-cell
RNA-sequencing approach. Our proposed studies will reveal genes that repair DNA lesions caused by alcohol
and its toxic metabolic by-products. It will also inform us how aged HSCs respond differently to alcohol-induced
DNA damage than younger HSCs. Identification of key differences in DNA damage response and DNA repair in
aged HSCs will enable us to uncover ways to prevent aging due to alcohol and potentially due to other
endogenous and exogenous DNA damaging agents as well.

## Key facts

- **NIH application ID:** 10930959
- **Project number:** 5R21AA030864-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Moonjung Jung
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,453
- **Award type:** 5
- **Project period:** 2023-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930959

## Citation

> US National Institutes of Health, RePORTER application 10930959, Understanding the aging process in hematopoietic stem cells by alcohol-induced DNA damage (5R21AA030864-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10930959. Licensed CC0.

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