# Interventions Testing Program at UM

> **NIH NIH U01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $1,553,900

## Abstract

ABSTRACT
Identification of interventions that extend mouse lifespan provides new insights into mechanisms
of longevity determination in mammals, and may lay the groundwork for eventual anti-aging
therapies in humans. The NIA Interventions Testing Program (ITP) evaluates agents proposed
to extend mouse lifespan by retardation of aging or postponement of late life diseases.
Interventions proposed by multiple collaborating scientists from the research community are
tested, in parallel, at three sites (Jackson Laboratories, University of Michigan and University of
Texas), using very similar, standardized protocols, and using sufficient numbers of genetically
heterogeneous mice to provide 80% power for detecting changes in lifespan of 10%, for either
sex, after pooling data from any two of the test sites. One hundred and two such lifespan
experiments, involving various doses of 66 distinct agents, have been initiated in the first twenty
years of the ITP. Thirty-six experiments have involved comparative tests of multiple doses of
effective agents, variable starting ages, or alternative dosing schedules. Statistically significant
effects on longevity, in one or both sexes, have been documented and then confirmed for
NDGA, rapamycin, acarbose, 17-α-estradiol (17aE2), and canagliflozin. Significant effects were
also noted for Protandim, glycine, meclizine, captopril, and astaxanthin. Lifespan trials are now
underway for 25 new agents. ITP survival results have also documented longevity benefits from
four agents started in middle-age: rapamycin, acarbose, 17aE2, and canagliflozin. A
Collaborative Interactions Program (CIP) has provided tissues from ITP drug-treated mice to an
open, growing, international network of scientific collaborators, meeting 26 requests from 17
distinct laboratories in the previous five-year period. Plans for the next five-year period include
additional lifespan ("Stage 1") trials, detailed analyses ("Stage 2") of agents found to increase
lifespan, transition from the CIP to an Interventions Biospecimens Repository, additional
diagnostic specificity in pathological assessments, inclusion of RNA-Seq data in all Stage 2
protocols, and comprehensive pharmacokinetic assessments of drugs found to increase
lifespan, as well as continued collaborative work with a network of scientists to study drug
effects on postulated aging mechanisms and links to disease. Site-specific studies at Michigan
will add a battery of tests for Aging Rate Indicators in fat, muscle, brain, plasma, and liver of
Stage 2 mice, and include tests of drug effects on learning and memory in Stage 2 protocols.
The work proposed should allow the ITP to continue to make major contributions to mammalian
aging biology.

## Key facts

- **NIH application ID:** 10876097
- **Project number:** 2U01AG022303-21
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** RICHARD A MILLER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,553,900
- **Award type:** 2
- **Project period:** 2003-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876097

## Citation

> US National Institutes of Health, RePORTER application 10876097, Interventions Testing Program at UM (2U01AG022303-21). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10876097. Licensed CC0.

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