# C. Elegans as a Model of Cell Senescence and Alzheimer's Disease

> **NIH NIH R21** · UNIVERSITY OF COLORADO · 2021 · $143,650

## Abstract

PROJECT SUMMARY/ABSTRACT
Significance: Cell senescence is implicated in many age-related diseases. Drugs which
postpone or reverse cellular senescence (SENO drugs) have been developed and three of these
drugs are in human clinical trials. The availability of an inexpensive, whole-animal model of SENO
drug action will accelerate development of new treatments of Alzheimer’s Disease.
Background: SENO drugs ameliorate numerous age-related pathologies through a common
pharmacological action: the selective killing or alteration of senescent cells. SENO drugs are
expected to postpone diverse causes of human mortality including Parkinson’s Disease,
Alzheimer’s Disease, and atherosclerosis, as well as cancer metastasis and recurrence. We
propose to study SENO drugs, targeting three distinct pathways. These pathways lead to
alternative responses characterized by distinct levels of AMP Kinase and P53.
C. elegans transgenic strains have been engineered to express the amyloidogenic human
proteins amyloid-beta (Aβ) and tau. We found that treatment with a SENO drug (piperlongumine)
resulted in longer life in the wild-type and postponed paralysis in Aβ-expressing transgenic worm
strains, and have since found a similar effect with a second SENO drug (KU60019). We propose
to extend these studies by applying a representative set of five SENO drugs to wild-type
nematodes and then apply single-cell RNA-Seq, to search for common seno-drug-driven
transcriptional changes within and between specific cell types.
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## Key facts

- **NIH application ID:** 10418204
- **Project number:** 3R21AG067147-02S1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** James R Cypser
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $143,650
- **Award type:** 3
- **Project period:** 2020-09-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418204

## Citation

> US National Institutes of Health, RePORTER application 10418204, C. Elegans as a Model of Cell Senescence and Alzheimer's Disease (3R21AG067147-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10418204. Licensed CC0.

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