Why the Interventions Testing Program (ITP) Is the Gold Standard for Longevity Research

https://www.nia.nih.gov/research/dab/interventions-testing-program-itp/supported-interventions

If youā€™re following the latest trends in longevity research, youā€™ve probably heard about a few ā€œmiracle compoundsā€ like metformin, resveratrol, and NAD boosters. But letā€™s get realā€”when it comes to real preclinical data that actually holds up, nothing beats the Interventions Testing Program (ITP). And no, weā€™re not here to play along with the hype around these compounds that often donā€™t deliver in the lab.

What Is the ITP and Why Should You Care?

The Interventions Testing Program (ITP), run by the National Institute on Aging (NIA), is a uniquely well-designed testing platform that focuses on evaluating the effects of different compounds on lifespan and healthspan in outbred mice (meaning they have genetic diversity more like human populations, unlike the typical inbred strains). This gives the data more translational potentialā€”interventions likely to work in humans are more likely to show efficacy in these outbred, well-powered experiments. This means the results arenā€™t confined to niche genetic conditions. The studies are conducted across multiple independent sites to ensure reproducibility and robustness of the data. Large sample sizes and rigorous methodology make this program a powerhouse for reliable preclinical results. If an intervention can work here, especially across different sites and genetically diverse mice, itā€™s hitting on something fundamental, not just a quirk of a specific strain or environment.

Metformin, Resveratrol, and NAD: Why Weā€™re Not Impressed

Letā€™s get into why some of these so-called longevity wonder drugs donā€™t quite live up to their reputations:

Metformin: While metformin has shown promise for managing glucose levels in type 2 diabetes, the data for longevity just doesnā€™t hold up. Large human clinical studies have failed to show any clear lifespan-extending benefits in healthy individuals. The ITP didnā€™t find significant longevity effects either, so while itā€™s a great tool for diabetes management, itā€™s not the fountain of youth people hoped for. Move on former mentor of mine I wonā€™t be namingā€¦ move onā€¦

Resveratrol: Remember when resveratrol was the darling of longevity science? With its cough ā€œtoo-good-to-be-trueā€ lab data, it got people excited about its potential anti-aging propertiesā€”until the ITP results showed no significant impact on lifespanā€¦ And labs that werenā€™t financially invested didnā€™t show impact on lifespanā€¦ And then the original lab results were shown to be a bit too niceā€¦ and thenā€¦ Ya, itā€™s all BS. Go check retraction watch or some other forum that hunts for data manipulation. The Red flags are R-E-D and its not from a wine stainā€¦

NAD Boosters: NAD boosters are the latest fad, but hereā€™s where it gets funny: the same people (personā€¦ but letā€™s say ā€œpeopleā€ for legal reasons) behind resveratrol are now pushing NAD as the next big thing. Fool me once with resveratrol, fool me twice with NAD? The ITP currently hasnā€™t looked at any NAD boosters other than Nicotinamide Riboside (NR) but that showed no impact and operates in the same pathway as NMN and NAD. I wonā€™t be holding my breath. Until compelling work of ITP caliber shows that boosting NAD+ levels leads to a longer life, itā€™s best to be skeptical until more solid data emerges.

Rapamycin and Acarbose: The True Stars of the ITP

Now letā€™s talk about the real heroes of the ITP: rapamycin and acarbose. These are the compounds you should be hyped about, and the data to back it up is strong.

Rapamycin: If thereā€™s one compound thatā€™s consistently shown to extend lifespan, itā€™s rapamycin. Rapamycin works by inhibiting the mTOR pathway, which is a core regulator of growth, metabolism, and aging. Whatā€™s exciting about rapamycin is that it works not just in mice, but across a broad range of organismsā€”C. elegans, fruit flies, yeast, and even mammals. This isnā€™t some niche treatment that only works in tightly controlled conditionsā€”it targets a fundamental mechanism in aging. Itā€™s the real deal.

Acarbose: Often overshadowed by rapamycin, acarbose has also shown significant lifespan extension in the ITP, especially in male mice. Acarbose works by slowing carbohydrate digestion and preventing large post-meal glucose spikes. And hereā€™s the kicker: rapamycin and acarbose seem to work synergisticallyā€”theyā€™re even more effective together than they are alone, suggesting they target different but complementary pathways involved in aging and metabolism.

Both these drugs have shown impressive lifespan extension through the ITP and they play together nicely as well! See here: https://pubmed.ncbi.nlm.nih.gov/36179270/.

Anyway, cool list of drugs right? Anything on the in process list that catches you eye? Any surprises revelations? What should be next?