# Investigating Cellular Senescence at the Single Cell Level

> **NIH NIH F30** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2024 · $53,974

## Abstract

Project Summary/Abstract
Aging is a key risk factor for chronic disease development which can affect lifespan and quality of life. Cellular
senescence has emerged as a potential target to slow down the aging process. Senescent cells are in a state of
proliferative arrest and are highly associated with aging and pathological conditions. They accumulate in multiple
tissues and secrete pro-inflammatory cytokines and other kinds of molecules that damage surrounding tissues.
The markers p16 and p21 (cyclin dependent kinase inhibitors) are commonly used to identify senescent cells,
but emerging evidence has shown that these markers are not entirely sensitive or specific markers for
senescence. There is currently a lack of understanding of the exact genetic markers that define senescent cells
especially on the single cell level. With studies showing that senescent cell clearance can alleviate various
diseases associated with aging it is vital to achieve a greater understanding of senescent cell markers so that
precision medicine treatments can be designed to more effectively eliminate senescent cells. In this proposal
we aim to examine the transcriptome of senescent cells on the single cell level both with aging and
senolytic treatment in human adipose tissues. Senescent cells have been demonstrated to accumulate in
adipose tissue with aging and chronic disease and with the vast array of cell types present in adipose tissue it
makes an excellent model to study specific cell types and markers associated with senescence. Aim 1 will
explore the transcriptome of naturally occurring senescent cell populations in adipose tissue with aging.
We will use single nucleus RNA sequencing to capture cell types sensitive to typical single cell dissociation
methods and compare the transcriptome differences between cells in aged vs. young tissues. We hypothesize
that adipose tissue from older donors will contain more senescent cells and that several novel genetic markers
will be identified in these cells. Aim 2 will look at the effects of senolytic treatment on human adipose tissue
on the single cell level. Senolytics are drugs that are designed to specifically eliminate senescent cells but we
do not know the precise cell types targeted by senolytics. We will use single nucleus RNA sequencing to uncover
the transcriptome changes that occur with senescent cell elimination and learn what cell types are removed with
senolytic treatment. This project will help advance the field achieving a greater understanding of senescent cell
populations in adipose tissue and the markers that define them, which is essential to understanding and
potentially treating numerous diseases. Through this fellowship my training will include developing my skills in
genetics, aging, computational analysis, communication, presentation, networking, scientific writing, clinical
knowledge and mentorship. This training will occur in the environment of UCONN Health as well as the Jackson
Laboratory and o...

## Key facts

- **NIH application ID:** 10857137
- **Project number:** 5F30AG081093-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Rachel Cohn
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2023-06-15 → 2026-06-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10857137

## Citation

> US National Institutes of Health, RePORTER application 10857137, Investigating Cellular Senescence at the Single Cell Level (5F30AG081093-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10857137. Licensed CC0.

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