The calibrated prior for 'we reversed aging in mice': near zero - and here's the arithmeticThe calibrated prior for 'we reversed aging in mice': near zero - and here's the arithmetic

Every few weeks a headline announces that scientists reversed aging, extended lifespan, or found 'the protein that ages your brain.' Before believing any single one, it helps to know the base rate. Here is the arithmetic from the most rigorous public dataset in the field.

The NIA Interventions Testing Program (ITP) tests candidate longevity compounds in genetically diverse mice, in parallel at three independent labs, specifically to weed out single-lab and single-strain flukes. Two numbers matter:

• Of the ~35 compounds it has tested, only about 8 significantly extended lifespan in at least one sex - roughly 1 in 4. And most of those wins are small and sex-specific: one drug added ~22% of median lifespan in males but only ~5% in females; another added just 4-5% in females, with the male signal confounded by an unusually short-lived control group at one of the three sites.
• Of those ~8 mouse winners, the number with a proven human lifespan or healthspan benefit on a hard clinical endpoint is zero. The only one with a dedicated human longevity trial (rapamycin, the PEARL trial) reported mainly safety, not a demonstrated anti-aging effect.

So the funnel from 'promising candidate' to 'proven human benefit' runs from about 23% to 0%.

Two honest caveats, because they matter. First, that 0% is partly because you cannot run a decades-long human-lifespan trial - 'not proven yet' is not the same as 'failed.' Second, this is not a claim that aging biology is fake; tissue-level mechanisms are real. The right takeaway is calibration: treat any single mouse headline as a low-probability bet on a proven human benefit within a decade, and expect the eventual human effect to be far smaller than the mouse result.

Why so low? Three measurable reasons.

1. 1. The verdict can depend on the statistic you choose. We simulated mouse survival data with an age-localized benefit (helps early, fades with age): the standard log-rank test and the Gehan-Wilcoxon test disagreed on whether the compound 'worked' on about 40% of identical datasets, and reporting the best of three tests inflated the false-positive rate from 5% to about 8%.
2. 2. The biomarker can move while the outcome doesn't. The clearest 2026 example: a supplement (NMN) reliably doubles a blood marker (NAD+), yet meta-analyses of randomized trials show no benefit to muscle or metabolism - and new work finds that blood marker doesn't even decline with age in humans. The gauge moved; the outcome didn't.
3. 3. Effects shrink and fragment across sex, strain, and lab.

Method, in two sentences: we took the ITP's published results and the human-trial record as the population and computed the pass rate at each stage; separately, we simulated weighted survival tests (log-rank, Gehan-Wilcoxon, Tarone-Ware) on age-localized effects to measure how often the 'works/null' verdict flips with the test choice.

What would change our mind: a hard-endpoint human result from any current mouse-stage longevity hit (a positive successor to PEARL, a positive metformin TAME trial, or a human signal from a newer target) would push the base rate up, and we would update.

This is not pessimism about longevity science. It is a calibrated prior - the number you should carry into the next headline.