# Optimizing resilience assays for biology of aging research in mice

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $342,350

## Abstract

Proposal Summary
Evaluation of lifespan and healthspan remain a cornerstone of documenting efficacy in aging research. However,
it is becoming increasingly appreciated that housing rodents in conventional, unprovoked conditions, rather than
exposed to the same variety of stressors normally encountered by free-living humans, has limited our
understanding of how these strategies can be most effectively translated to humans. As defined in this RFA
resilience is the ability in which an organism can respond to a physical challenge or stress and return to
homeostasis. Physiologic resilience declines with age and can contributes to, and may underlie the onset of
aging-related conditions. Thus, resilience in early or mid-life may be predictive of future healthspan and longevity.
Thus, development of a simple, short-term battery of assays to characterize resilience in rodents could
revolutionize aging research by enabling a rapid, inexpensive and comprehensive strategy to diagnose
intervention efficacy, with possible prediction value for future outcomes. Therefore, we propose a battery of
simple, diverse challenges and assays to include elective surgery, radiation, starvation, and an infection model
to characterize resilience in rodents with the goal of predicting future outcomes. We hypothesize that exceptional
resilience is requisite to healthy aging and longevity, and that assays optimized to detect variation in resilience
can be prognostic of long-term aging outcomes. In Aim 1, we will establish and optimize a battery of functional
tests to distinguish changes in physiologic resilience with aging in CB6F1 male and female mice. The goal of
this aim is to calibrate both the application and detection of responses to stressors with well-established human
homologues (radiation, starvation, surgery, and infection) and straight-forward response assays (i.e. body
weight, temperature, etc) in mice at 4, 12, and 20 mo of age. We will consider implementation successful with
observed age sensitivity to the stressor and increasing intra-group variability in the response with advancing age,
which will confirm the potential for discriminating good, average and poor responders as a predictor of outcomes
in Aim 2. In Aim 2, we will determine the ability of resilience at 12 mo of age to predict future healthspan across
multiple domains (cognitive, cardiovascular, neuromuscular, metabolic) as well as longevity. In Aim 3, we will
determine if pharmacologic interventions with demonstrated sexually-dimorphic effects on aging outcomes
confer similar sex differences in physiologic resilience. This Aim will attempt to validate the ability of optimized
tests of resilience to interventions that modulate lifespan by focusing on two pharmacologic strategies with
striking sex differences on survival. To that end, 16 mo old male and female mice for 4 mo with 17α-estradiol,
which preferentially favors males, and IGF-1R mAb, which favors females, and determine if sex-specific
improve...

## Key facts

- **NIH application ID:** 10166753
- **Project number:** 5R01AG057429-06
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** DEREK Major HUFFMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $342,350
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166753

## Citation

> US National Institutes of Health, RePORTER application 10166753, Optimizing resilience assays for biology of aging research in mice (5R01AG057429-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166753. Licensed CC0.

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