# Aging and Resiliency in Mice: Optimizing Assessment Protocols and Testing Interventions

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2020 · $396,364

## Abstract

PROJECT SUMMARY/ABSTRACT
Therapeutic interventions that target fundamental mechanisms of aging are being sought to radically transform
public health. Indicators of biological aging that can be identified prior to overt manifestations of late-life
conditions, and concomitantly serve as predictors of future health and longevity, could facilitate this effort. As
highlighted in this RFA, resilience, defined as the ability of an organism to adequately respond to physical
challenges, may offer one such opportunity. Thus, the objective of this proposal is to develop and validate a
battery of disease-agnostic physical challenges to enable the evaluation of resiliency in mice. To this end, in
Specific Aim 1 we will determine which physical challenges best reveal differences in resilience between and
within younger, middle-aged, and older mice. Specifically, we will assess acute responses to anesthesia,
chemotherapy, surgery, and dehydration in cohorts of 4-month-old, 12-month-old, and 20-month-old mice. In
Specific Aim 2, using the physical challenges deemed optimal in Specific Aim 1, we will determine the extent to
which baseline resilience of middle-aged mice longitudinally predicts healthspan using discriminating measures
of physical, metabolic, cardiovascular, and immune function at Mayo Clinic, and lifespan at the University of
Michigan. Given the considerable evidence that aberrant mTOR signaling and senescent cell accumulation are
mediators of aging, in Specific Aim 3 we will determine the extent to which rapamycin and targeted clearance
of p16INK4a-positive senescent cells affect the resilience of older mice to physical challenges. We expect that a
standardized battery of clinically relevant measures of resilience in laboratory mice will provide a new
framework in which to test innovative and potentially transformative interventions to promote healthy aging. In
humans, the emergence of chronic diseases and syndromes such as frailty may reflect a point of no return.
Compromised resilience earlier in life, on the other hand, may ultimately serve as a therapeutic opportunity in
which the progression of aging-related molecular and cellular damage can be attenuated, if not reversed.

## Key facts

- **NIH application ID:** 9918217
- **Project number:** 5R01AG053832-05
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Nathan K LeBrasseur
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,364
- **Award type:** 5
- **Project period:** 2016-08-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918217

## Citation

> US National Institutes of Health, RePORTER application 9918217, Aging and Resiliency in Mice: Optimizing Assessment Protocols and Testing Interventions (5R01AG053832-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9918217. Licensed CC0.

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