Rapamycin+Acarbose Increases Lifespan 30% in mice
A 2022 study of various drugs, found that the combination of rapamycin plus acarbose in genetically heterogeneous mice profoundly increased lifespan. This combination of agents produced a 28% increase in median lifespan in females (p < 0.0001) and a 34% increase in males (p < 0.0001) for data pooled across multiple experimental sites (To remove site specific confounders). This was the only treatment that significantly increased survival in both sexes at all test sites. [1]
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Another 2022 article found that a cocktail of rapamycin, acarbose and phenylbutyrate showed a dose-specific (14 ppm rapamycin, 1000 ppm acarbose, and 1000 ppm phenylbutyrate) improvement in inflammation, physiological performance, and measurable aging changes.[2] This experiment did not test total lifespan, but measures of health instead.
Of course, rapamycin by itself can have some known bad side effects like glucose intolerance and insulin resistance, so the antidiabetic drugs metformin and acarbose may be acting beneficially, at least partially, by alleviating that. [3]
To put this in perspective, you can use rapamycin plus many other drugs and often get some synergistic effect. Here is an article where they tested Rapamycin plus Trametinib and got a 30% lifespan increase for male mice. (and since Rapamycin raises A1C/sugar it is often paired with diabetic drugs as well to offset that)
However, we are not mice, and many of these combos will likely not benefit humans by that same amount. And it may be useful to recall that you can increase the lifespan of a roundworm or fruit fly by 100-300% many times but these treatments do not have such large effects when tested on complex animals like a mouse. Likewise, things that have a big effect on mice do not necessarily have that large an effect on humans. It would be great to know why this is. Perhaps we are optimized quite a bit already.
References
[1] Strong, R., Miller, R. A., Cheng, C. J., Nelson, J. F., Gelfond, J., Allani, S. K., Diaz, V., Dorigatti, A. O., Dorigatti, J., Fernandez, E., Galecki, A., Ginsburg, B., Hamilton, K. L., Javors, M. A., Kornfeld, K., Kaeberlein, M., Kumar, S., Lombard, D. B., Lopez-Cruzan, M., ... Harrison, D. E. (2022). Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice. Aging Cell, 21(12), Article e13724. https://doi.org/10.1111/acel.13724
[2] Jiang, Z., Wang, J., Imai, D. et al. Short term treatment with a cocktail of rapamycin, acarbose and phenylbutyrate delays aging phenotypes in mice. Sci Rep 12, 7300 (2022). https://doi.org/10.1038/s41598-022-11229-1
[3] https://www.nature.com/articles/s43587-023-00489-9#Tab3
[4] https://www.lifespan.io/news/a-drug-combo-increases-lifespan-in-mice-by-over-30/
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