# Physical resilience is a predictor of healthy aging in mice

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $317,750

## Abstract

Physical resilience is a predictor of healthy aging in mice
Abstract
Physical resilience is the ability of an organism to respond to physical stress, and can be measured with
various types of stress tests. The loss of resilience occurs much earlier than the development of frailty. Thus,
loss of resilience may result in age-related frailty. When measuring overall resilience, integrative responses
involving multiple tissues, organs, and activities are desirable, so as to inform about the overall health status of
the animal. Therefore, it is more likely that a battery of stress tests, rather than a single all-encompassing one,
will be more informative. An ideal battery of tests should have enough dynamic range in the response to allow
characterization of an individual in easily distinguishable groups as being resilient or non-resilient. We have
selected three stressors, cold, sleep deprivation and the chemotherapeutic drug cyclophosphamide, to
investigate based on features of duplication as well as translational relevance. People develop intolerance to
cold with increased sensitivity to hypothermia with increasing age. The mechanisms of response to cold are
multifactorial. Sleep deprivation is a major health concern in developed countries and is associated with
increasing age, and is a risk factor for insulin resistance and diabetes and memory loss. About one third of
people in developed countries experience some type of chemotherapy in their lifetime, and cyclophosphamide
is an excellent representative chemotherapeutic agent to test resilience because it is used extensively in
patients for a variety of conditions including cancer and rheumatoid arthritis. It targets several different systems
but most specifically the hematopoietic system. The hypothesis of this proposal is that a physical stress
test panel of cold, sleep deprivation and cyclophosphamide will measure resilience and predict healthy
aging in mice. Three specific aims have been developed to address this hypothesis. Aim 1 will validate
resilience parameters. Mice at middle age will be challenged with cold, sleep deprivation, and
cyclophosphamide, and assessed with physiological and histological measurements in order to establish
intensity and a sequence for administering the stress test panel. Aim 2 will investigate age-dependent
resilience. Mice at different ages will be challenged with cold, sleep deprivation, and cyclophosphamide, and
assessed with physiological and histological measurements in order to establish a base line for dose response
that aligns with biological age. Aim 3 will determine the ability of the stress panel to measure resilience as an
endpoint to an anti-aging drug. For this, we have selected rapamycin because it is well documented in
extending lifespan and enhancing health span in mice, and also because we have experience with the drug in
mouse aging studies. The result of this proposal will be the development of resilience as a translational aging
signature prov...

## Key facts

- **NIH application ID:** 10166752
- **Project number:** 5R01AG057381-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Warren C LADIGES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $317,750
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166752

## Citation

> US National Institutes of Health, RePORTER application 10166752, Physical resilience is a predictor of healthy aging in mice (5R01AG057381-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10166752. Licensed CC0.

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