Scientists test potential health- and lifespan-extending interventions in model organisms like mice to evaluate their effectiveness. The Interventions Testing Program (ITP), a federally funded initiative, conducts unbiased tests on various drugs to identify potential longevity interventions for humans. Matt reviews recent ITP tests on compounds like alpha-ketoglutarate, hydralazine, and canagliflozin, discussing their effects on lifespan, gender differences, and the importance of control group life expectancy in evaluating results.

Key Points:

Matt explains that scientists start by testing interventions in model organisms like mice to gauge their potential health and lifespan benefits, as done through the Interventions Testing Program (ITP). The ITP tests various drugs on mouse ageing, aiming to identify promising longevity treatments for humans.

• Interventions Testing Program (ITP): A federally funded program designed to identify drugs that increase lifespan in mice, offering a gold standard for testing longevity interventions.
• 2020 Cohort Results: Out of eight drugs tested, two showed positive effects on lifespan—16α-hydroxyestriol and canagliflozin—though with gender-specific results.
• Key Drugs and Findings: 16α-hydroxyestriol extended lifespan in male mice but decreased it in females. Similarly, canagliflozin, when started late, extended lifespan in males but reduced it in females.
• Sex-Specific Effects: Most drugs tested showed lifespan effects that were gender-specific, highlighting a significant gap in understanding why males and females respond differently.
• Failures in 2020: Drugs like alpha-ketoglutarate, 2,4-dinitrophenol, hydralazine, and nebivolol did not show significant lifespan benefits, reducing enthusiasm for their longevity potential.
• Future Outlook: While 16α-hydroxyestriol and canagliflozin are promising, the need for better mechanistic understanding of sex-specific effects and expansion of rigorous testing is emphasized.