# A sex difference approach to evaluating resilience as a predictor of healthspan in mice

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $304,425

## Abstract

Project Summary
 Aging of the human population has become the number one threat to human health globally as life
expectancy is rising rapidly and because aging underlies nearly all major causes of death, disability, and
degradation of the quality of later life. Hope for amelioration of this trend lies with the development of
treatments that enhance and extend health. A major limitation on evaluating promising compounds for their
senescence-inhibiting properties is the time it takes to perform lifespan studies in mice, the main preclinical
animal model employed in biomedical research. Similarly, once compounds are ready for human testing, the
time it takes to complete clinical trials will also become a bottleneck. In order to speed progress in the field
then, it would be invaluable to develop a panel of short-term assays that could be administered to mice in
early- to mid-life that would predict whether or not an intervention will extend healthspan in mice. The ability of
an organism to recover from acute physical challenges or stresses is well-known to decline with age. If we
define resilience as a quantitative metric which gauges the ability and speed of an organism to return to
homeostasis after physical stress or challenge, then life- and health-extending interventions generally enhance
resilience. The goal of the proposed research is to develop a standardized challenge or panel of challenges
and their accompanying recovery metrics that will be informative about the healthspan impact of putative
health-extending interventions when administered in early-to-mid life. The overarching hypothesis of the
proposed research is that resilience assays can be developed that singly, or in combination, predict future life-
and/or health-span. We propose to evaluate our overarching hypothesis purposely focusing on resilience
assays with translational potential by performing the following specific aims (SAs). SA 1 will optimize resilience
assay protocols, each consisting of an acute physical challenge and associated recovery metrics as to the best
age and severity of challenge to use. SA 2 will determine whether the resilience assays optimized in specific
aim 1 can identify the impact of known life- or health-span extension treatments. Three such treatments will be
compared to untreated controls. These are: (a) dietary restriction (DR). This can be thought of as a positive
control. To be informative, our resilience assays should predict longer life in both sexes; (b) rapamycin, our
resilience assays should predict longer life in both sexes, but a greater effect in females; and (c) 17-α-estradiol.
Our resilience assays should predict longer life in males only. SA 3 will evaluate the robustness of the most
successful resilience assays identified in specific aim 2 across mouse genotypes. Because humans are so
genetically and environmentally diverse, the generality of mouse assays should be maximized to the extent
possible. Diverse mouse genotypes are available ...

## Key facts

- **NIH application ID:** 10166754
- **Project number:** 5R01AG057434-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** STEVEN N. AUSTAD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $304,425
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166754

## Citation

> US National Institutes of Health, RePORTER application 10166754, A sex difference approach to evaluating resilience as a predictor of healthspan in mice (5R01AG057434-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166754. Licensed CC0.

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