# Probing relationships between DNA methylation and cellular senescence with high-throughput CRISPR-based epigenetic editing

> **NIH NIH R21** · STANFORD UNIVERSITY · 2023 · $193,844

## Abstract

ABSTRACT
 Cellular senescence is a phenomenon associated with aging, wherein cells stop proliferating and secrete
factors which may impact the function of surrounding cells and tissues. Although epigenetic readouts, and in
particular DNA methylation (CpGme), have found to be associated with aging and cellular senescence, it remains
undetermined whether accumulated changes in CpGme are merely correlated with senescence or whether they
play a causal role in driving it. To answer this question, we will combine next-generation sequencing techniques
along with CRISPR-based CpGme editing and CRISPR screens to elucidate the causative associations between
CpGme sites across the genome and cellular senescence.
 In Aim 1, we will assess CpGme sites of interest for effect on cellular senescence with a high-throughput
CRISPR screen. Using a CRISPR molecule capable of depositing CpGme, it is possible to generate a population
of cells, each with CpGme modified at a particular site. By characterizing how these CpGme modifications
influence the entry rate into senescence, we will identify CpGme sites that causally affect senescence.
 In Aim 2, we will dissect how the most active sites operate to affect senescence. This will be done by inducing
CpGme at the target sites and observing how this influences genomic CpGme and gene expression profiles,
which will provide mechanistic understanding of how the perturbations we make affect cellular function. We will
develop methods to more broadly apply CpGme editing to control cellular senescence. The work will illuminate
an important process associated with aging and will provide new tools to for understanding how epigenetics
impacts biological function, as well as how we can engineer cells to optimize health in the future.

## Key facts

- **NIH application ID:** 10593233
- **Project number:** 1R21AG077193-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lei Stanley Qi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $193,844
- **Award type:** 1
- **Project period:** 2022-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10593233

## Citation

> US National Institutes of Health, RePORTER application 10593233, Probing relationships between DNA methylation and cellular senescence with high-throughput CRISPR-based epigenetic editing (1R21AG077193-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10593233. Licensed CC0.

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