ITP Longevity Breakthroughs: 2BAct, Halofuginone and DCA Extend Lifespan in Mice

TL;DR: In 2025, the NIA Interventions Testing Program (ITP) published a landmark study from its 2021 mouse cohort. Three compounds — epicatechin, halofuginone and mitoglitazone — significantly extended lifespan in male, but not female, genetically heterogeneous mice. 2BAct and dichloroacetate (DCA) were also tested in the same cohort. These are rigorous mouse results, but mouse lifespan extension often fails to translate to humans.

1. What Is the Interventions Testing Program?

The National Institute on Aging Interventions Testing Program (ITP) is the gold-standard preclinical platform for testing lifespan-extending drugs. It was set up to overcome the problem of unreproducible single-lab mouse studies.

Key features:

• Genetically heterogeneous mice: UM-HET3 mice are deliberately bred to mimic human genetic diversity, unlike inbred strains.
• Three independent labs: each compound is tested simultaneously at Jackson Laboratory, the University of Michigan and the University of Texas Health Science Center at San Antonio.
• Blinded, randomised design: treatments are mixed into feed and compared to matched controls.
• Lifespan and healthspan endpoints: the main readout is median and maximum lifespan, with secondary measures of body weight, pathology and, in some cases, tissue function.

Because of this design, a positive ITP result carries far more weight than a single-lab finding. But it is still mice.

2. The 2021 ITP Cohort Results

The 2025 GeroScience paper reported lifespan effects in mice bred in 2021 and treated with 2BAct, dichloroacetate, epicatechin, forskolin, halofuginone and mitoglitazone (Strong et al., 2025).

Compounds that extended lifespan in male mice

• Epicatechin: a cocoa/tea flavonoid that improved median and maximum lifespan in males. It has been linked to mitochondrial biogenesis, NO signalling and reduced oxidative stress in prior work.
• Halofuginone: a plant alkaloid derivative that acts as a prolyl-tRNA synthetase inhibitor and mimics amino-acid restriction. It reduced mTOR pathway activity and extended lifespan in males.
• Mitoglitazone: a PPARγ/mitochondrial-targeted compound related to the thiazolidinedione class. It extended lifespan in males, possibly through improved metabolic health.

Compounds that did not significantly extend lifespan

• 2BAct (2BA): an integrated stress response (ISR) inhibitor developed to protect neurons from protein-synthesis shutdown. It was included in the cohort but did not show a statistically significant lifespan extension in this report.
• Dichloroacetate (DCA): a metabolic modifier that shifts cells toward oxidative glucose metabolism by inhibiting pyruvate dehydrogenase kinase. It also did not significantly extend lifespan in this ITP cohort, though it has shown positive effects in other models.
• Forskolin: a cAMP-elevating plant compound. No lifespan benefit was detected.

3. Why Did Only Males Benefit?

Sex differences are common in ITP studies. Male and female mice differ in metabolism, immune function, hormone signalling and baseline inflammation. A compound that corrects a male-specific deficit may not help females, and vice versa.

This sex-specificity is one reason mouse results are so hard to translate. If the benefit depends on male mouse biology, it may not apply to women, to older men with different hormone profiles, or to people with diverse genetics.

4. Mechanisms in Brief

• Halofuginone: inhibits prolyl-tRNA synthetase, activating the amino-acid starvation response and suppressing mTORC1 — similar in logic to rapamycin or dietary restriction.
• Epicatechin: increases nitric oxide bioavailability, supports mitochondrial function and may reduce oxidative stress in muscle and vasculature.
• Mitoglitazone: improves insulin sensitivity and mitochondrial quality through PPARγ-related mechanisms.
• 2BAct: blocks the integrated stress response kinase PKR-like ER kinase (PERK), preventing stress-induced translational shutdown in neurons.
• DCA: inhibits pyruvate dehydrogenase kinase, pushing pyruvate into the mitochondria and away from lactate production.

5. Availability, Safety and Caution

None of these compounds are approved for human anti-ageing use. Their status:

• Epicatechin: found in cocoa and green tea; sold as a research supplement, but ITP doses are not established for humans.
• Halofuginone: used in veterinary medicine and investigated for cancer/fibrosis; not a casual supplement.
• Mitoglitazone: investigational; not widely available as a supplement.
• 2BAct: preclinical; not available for human use.
• Dichloroacetate (DCA): an old metabolic drug used for some rare enzyme disorders; peripheral neuropathy is a known risk with long-term use.

6. References

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