# Interventions Testing Program at UM

> **NIH NIH U01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $1,382,816

## Abstract

Identification of small molecules 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 identical, 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. Seventy-two such lifespan
experiments, involving various doses of 44 distinct agents, have been initiated in the first fifteen
years of the ITP. Thirty-seven experiments have involved comparative tests of multiple doses of
effective agents, variable starting ages, or alternative dosing schedules. Significant effects on
longevity, in one or both sexes, have been documented and then confirmed for NDGA,
rapamycin, acarbose, and 17-α-estradiol (17aE2), with significant (but currently unconfirmed)
effects also noted for Protandim, glycine and, in an interim analysis, canagliflozin. Lifespan trials
are now underway for 18 new agents. ITP survival results have also documented longevity
benefits from three agents started in middle-age: rapamycin, acarbose, and 17aE2. The
previous five year period has introduced three new features to the ITP: increased emphasis on
health outcomes (functional tests relevant to human health not necessarily linked to lifespan), a
Collaborative Interactions Program to provide tissues from ITP drug-treated mice to an open,
growing, international network of scientific collaborators, and a publicly accessible data
repository and display engine hosted by the Mouse Phenome Database at the Jackson
Laboratory. Plans for the next five-year period include additional lifespan ("Stage I") trials,
detailed analyses ("Stage II") of agents found to increase lifespan, continued growth in data on
health outcomes, and collaborative work with scientists to study drug effects on postulated
aging mechanisms and links to disease. Studies at Michigan will follow up our analyses of
cellular pathways relevant to stress resistance and inflammation, by continuing ongoing studies
of cap-independent protein translation, chaperone mediated autophagy, and browning of white
adipose cells. The work proposed should allow the ITP to continue to make major contributions
to mammalian aging biology.

## Key facts

- **NIH application ID:** 10380685
- **Project number:** 5U01AG022303-19
- **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:** 2022
- **Award amount:** $1,382,816
- **Award type:** 5
- **Project period:** 2003-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380685

## Citation

> US National Institutes of Health, RePORTER application 10380685, Interventions Testing Program at UM (5U01AG022303-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380685. Licensed CC0.

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