# Using the senolytic fisetin to suppress mortality in aged mice acutely exposed to murine beta-coronavirus

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $169,400

## Abstract

Project Summary
Aging and the chronic diseases associated with aging place a tremendous burden on our healthcare system and
reduce quality of life for the elderly. As our world population ages dramatically over the next three decades, the
burden will only increase. Hence, there is a great need to discover fundamental mechanisms of aging to develop
rationale strategies for minimizing the impact of aging on our health and economy. This fostered the Geroscience
hypothesis, which posits that therapeutically targeting fundamental mechanisms of aging will yield a larger
dividend in terms of improving the health of an aging population than would treating individual age-related
diseases. The fundamental mechanism of aging where this has borne out most successfully to date is through
elimination of senescent cells. Senolytic drugs were first described by us and others in 2015 and have already
fostered multiple clinical trials beginning in 2018. In mice, senolytics improve physical function, tissue health and
suppress all cause mortality. COVID-19 has emerged as an urgent threat to our aged population.
 The goal of the parent project is to fully define the mechanism by which an aged / senescent immune system
drives morbidity and mortality using mice as a model organism. The goal of this revision is to use the knowledge
and resources we have to study the role of cellular senescence in driving adverse outcomes in aged organisms
acutely exposed to novel viral pathogens. Preliminary data indicate that mice with a substantial senescent cell
burden respond much worse to inflammatory challenges than mice without senescent cells. Furthermore,
exposure to normal pathogens carried by wild or pet store mice is sufficient to kill old experimental mice housed
in specified pathogen-free conditions, but it does not kill young mice. Here, we propose to use this experimental
paradigm to determine if senolytics, drugs that specifically kill senescent cells, suppress mortality in aged, obese,
diabetic or diseased mice. The immediate goal of this revision is to generate sufficient preclinical data to support
clinical trials using nutraceuticals with senolytic activity to prevent adverse outcomes in those at high risk of
COVID-19 infection or grave illness after infection. The long term goal of this project is to enable rigorously
testing the Geroscience hypothesis.

## Key facts

- **NIH application ID:** 10145445
- **Project number:** 3R01AG063543-02S1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** LAURA Jane NIEDERNHOFER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $169,400
- **Award type:** 3
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145445

## Citation

> US National Institutes of Health, RePORTER application 10145445, Using the senolytic fisetin to suppress mortality in aged mice acutely exposed to murine beta-coronavirus (3R01AG063543-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145445. Licensed CC0.

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