#281 ‒ Longevity drugs, aging biomarkers, and updated findings from the Interventions Testing Program (ITP) | Rich Miller, M.D., Ph.D.

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Dec 4, 2023

Rich Miller, a leading expert in aging research and Director at the University of Michigan’s Center for Aging Research, shares groundbreaking insights from the Interventions Testing Program (ITP). He reveals successful longevity drugs like rapamycin and the surprising failures of others, such as metformin. The conversation dives deep into aging biomarkers, highlighting their significance in understanding longevity. Miller also discusses the future of translating findings from mouse models to human applications, offering an optimistic vision for age-related research.

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INSIGHT

ITP Overview

The Interventions Testing Program (ITP) searches for aging-slowing drugs, primarily in mice.
It uses a unique, genetically diverse mouse model, UMHET3, unlike standard inbred models.

INSIGHT

Mouse Models

Standard Black 6 mice are inbred and homozygous, limiting their generalizability for research.
UMHET3 mice are genetically heterogeneous, offering reproducible diversity and enabling gene mapping.

INSIGHT

Study Metrics

The ITP primarily uses median and maximal lifespan as outcome measures.
Maximal lifespan is assessed at the 90th percentile of deaths, not the absolute last death.

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Richard Miller is a professor of pathology and the Director of the Center for Aging Research at the University of Michigan, as well as a previous guest on The Drive. In this episode, Rich provides an update on the exciting work of the Interventions Testing Program (ITP), an initiative designed to assess potential life-extending interventions in mice. Rich covers the notable successes like rapamycin, 17⍺-estradiol, and acarbose as well as notable failures like nicotinamide riboside, metformin, and resveratrol, providing valuable lessons about the intricacies of the aging process. Rich delves deep into aging biomarkers and aging rate indicators, unraveling crucial insights into the science of geroprotective molecules. Additionally, Rich discusses some surprising successes of recent molecules tested by the ITP and concludes with an optimistic look at future frontiers, including bridging the gap from mice to humans.

We discuss:

An overview of the Interventions Testing Program (ITP) [3:45];
How the mice used by the ITP are superior for research relative to mouse models used in most research [11:15];
Design of ITP studies, outcomes tested, and metrics of interest [19:00];
The process and challenges of drug formulation for mice [30:00];
Four drugs identified by the ITP that extends the lifespan of mice [36:30];
The success of rapamycin and what it tells us about the biology of aging [43:15];
Other measures of healthspan evaluated by the ITP in stage 2 studies [50:45];
Distinguishing aging rate indicators from biomarkers of aging [57:30];
Aging rate indicators identified through the examination of slow-aging mice [59:15];
Why proteomics are essential to understand changes in the cell [1:12:15];
Unraveling aging rate indicators: dose-effect, duration, and future frontiers [1:21:45];
A closer look at aging rate indicators: bridging the gap from mice to humans [1:27:00];
What do laboratory mice die from? [1:38:45];
Distinguishing between a drug that improves an age-sensitive outcome and a drug that improves all aspects of aging [1:42:00];
The ITP study of 17⍺-estradiol: mechanisms of life extension and surprising sex differences [1:43:30];
Unsuccessful drugs studied by the ITP: resveratrol, metformin, and nicotinamide riboside [1:51:30];
Over-the-counter successes in the ITP: meclizine and astaxanthin [2:01:00];
A senolytic drug, fisetin, fails to extend lifespan [2:07:00];
Can targeting senescent cells slow aging? [2:13:00];
Optimism about future findings [2:16:30]; and
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