Thread by @mkaeberlein

Here’s a detailed explanation with sources for my graphic illustrating potential effects of targeting aging with rapamycin in humans. This is based on a *speculative* extrapolation from mice to humans /1

The graphic represents impact on life expectancy for a typical 50 year old woman from curing cancer or heart disease and comparing it to potential impact from an intervention like rapamycin that targets biological aging. Green = healthy years, red represents unhealthy years /2

The calculations for effects on life expectancy from curing cancer or heart disease come from work done by Jay Olshanksy and colleagues published in Science here:

science.org/doi/10.1126/sc…

Original graphic here:

academic.oup.com/ppar/article/2…

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Dozens of independent studies report lifespan and age-related health benefits from rapamycin in mice, including reversal of deficits in multiple tissues. Average lifespan extension 9%-25%. At least two studies show big effects from transient treatments during middle-age.

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In my lab, we showed 12 weeks of rapamycin treatment from 20-23 months increased remaining life expectancy by up to 61%. This was the largest effect we saw. It was in males at the highest of 2 doses we tested

elifesciences.org/articles/16351…

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Work from Pan Zheng’s beautifully showed 6 weeks of rapamycin treatment in 22-24 month old mice rejuvenates the immune system. *Highly recommend* reading this paper. They also did a small survival experiment and found dramatically increased lifespan
ncbi.nlm.nih.gov/labs/pmc/artic…
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We don’t know how much this 6 week rapamycin regimen increases lifespan in mice because they didn’t finish the experiment, but it’s at least a doubling of remaining life expectancy (>100%).

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Median survival of the control mice is 15 weeks. Median survival of the rapamycin-treated mice is greater than 30 weeks. Maybe *much* greater (80% still alive!!!). So it’s at least a 100% increase in remaining life expectancy.

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Back to the graphic presenting possible effects in humans. If we assume this is a 50 year old woman, she will have ~30 years of life expectancy remaining. So, that’s at least 30 more years for the 50 year old woman, which is what's shown /9

When combined with the dozens of other studies showing rapamycin broadly improves health during aging in mice, I feel pretty comfortable suggesting that healthspan could also be greatly improved in aging people, as represented by the green shading

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To give you a glimpse, among the things rapamycin improves in aging mice are: cancers, cognitive function, heart, immune, kidney, oral health, intestine/gut dysbiosis, tendon, liver, auditory function, ovary…

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For now, evidence mostly comes from work in mice, with hints of potential benefits in companion animals and humans. Fortunately, we are starting to see baby steps toward clinical trials for rapamycin. Stay tuned, I expect you’ll be hearing a lot more on this in 2022

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