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

> **NIH NIH R21** · UNIVERSITY OF COLORADO · 2021 · $192,500

## 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.
Specific Aim 1. Determine if other SENO drugs suppress Aβ and/or tau toxicity.
Synopsis: We propose to monitor the efficacy of SENO drugs in the nematode C. elegans. We will utilize the
wild-type, as well as Aβ and tau transgenic strains. Several outcome parameters will be assessed:
amelioration of Aβ and tau toxicity, longevity, health-span, fertility, development, and analyses of behavior.
Specific Aim 2. Molecular studies of SENO action in C. elegans.
Synopsis: We will characterize the expression of P53 and AMPK in aging wild-type C. elegans with and
without the application of SENO drugs. Worms will be harvested at 4, 7, and 11 days of age. This will allow us
to compare the levels of these proteins in aging C. elegans due to SENO treatments, such as those in
senescent mammalian cells. C. elegans will lend itself well to detailed molecular studies consequent to our
findings.
Specific Aim 3. Transcriptome analysis by RNA-Seq.
Synopsis: RNA-Seq, using next-generation DNA sequencing, will be used to examine the transcriptome
changes in response to SENO drug treatments.

## Key facts

- **NIH application ID:** 10261332
- **Project number:** 5R21AG067147-02
- **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:** $192,500
- **Award type:** 5
- **Project period:** 2020-09-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261332

## Citation

> US National Institutes of Health, RePORTER application 10261332, C. Elegans as a Model of Cell Senescence and Alzheimer's Disease (5R21AG067147-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10261332. Licensed CC0.

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