Rapamycin, Acarbose and 17α-estradiol share common mechanisms regulating the MAPK pathways involved in intracellular signaling and inflammation

Another new research paper from Richard Miller and the ITP researchers:


So this is independent of the effects acarbose has on starch digestion? I was of the belief that this was its only way for providing longevity benefits. But maybe not.

1 Like

Yes - I find this very surprising. It also suggests that if the overlap on pathways is significant, we may not see much improvement if a person is taking all three compounds vs. just one.

Acarbose is so cheap. I wonder what new protocols this will encourage.

However, tbh when I’ve taken acarbose I’ve noticed none of the body high type of feelings I get while fasting or while on rapamycin or after senolytics, I think all of which are due to reducing inflammation. I wonder if the dose needed for similar effects would be much higher.

It’s surprising that Rapamycin, Acarbose and 17α-estradiol share common age-dependent pathway via MAPK pathways and MEK3/p38/MK2 pathway

It has seemed plausible that lower inflammatory tone could contribute to the exceptionally healthy lifespan of these mutant mice. Our work here shows that diminished production of inflammatory mediators is also characteristic of mice whose longevity is caused by treatment with Rapa, ACA, or 17aE2

It looks like that all 3 compounds extend lifespan by lowering inflammation state, suggesting that inflammation really plays a strong key in aging progress.

I am curious if there are other compounds that can extend lifespan not by lowering inflammation state, then that can the next breakthrough

It’s pretty cool that they have overlapping mechanisms, and they lower inflammation which is a hallmark of aging.

However I imagine that there is much to be said for the other not completely overlapping mechanisms too (e.g. mTOR, whatever 17-alphaestradiol does to men, etc.)

1 Like

Yes - its very interesting… but I wonder how big a role the inflammation truly is as an influence in aging… how do we explain the differential effects of 17 alpha estradiol in men vs. women? I’m assuming that inflammation in men is no different than inflammation in women…

We do need to remember that improvements in hallmarks of aging tend to be correlated with each other. Based on this, inflammation reduction should be expected of all longevity interventions. But that apart, it’s pretty interesting that MAPK is implicated in each of these 3 molecules.

So does it still work if you’re keto or eat fruit?

@shc could you expand on what you mean by a ‘body high’? Is this reflected in any acute bio markers, eg HRV or sleep

1 Like

Ah sorry I was reporting a subjective experience. But CRP levels I believe would be a good biomarker to capture this.

1 Like

I’ve had the same experience but had put it down to the placebo effect. It’s like having a double espresso