Rapamycin's primary effects include tamping down maladaptive inflammation via intermittent mTOR blunting, enhancing autophagy, and altering protein translation.

“maybe maybe i shouldn't say every all of the interventions that i know about that that i'm enthusiastic about translationally seem to hit inflammation in mice and they seem to tamp down on you know the chronic sterile inflammatory signaling that we see go along with aging which makes sense it's encouraging right that that they all seem to have this shared mechanism but the other the flip side of that is i'm i'm you know people talk a lot about their people are very excited now about you know analytics or reprogramming now is the new the news analytics right it's the thing everybody's excited about i'm not sure that those are fundamentally different from rapamycin in terms of the way that they're working and and i think we obviously we need to find out because you know it would be nice to know whether combinations of these interventions are going to do better than one alone but but to me the underlying theme that seems to be similar about all of these things that work in mice is if you look in tissues of aged mice at you know inflammatory cytokines p16 p21 markers of senescence they seem to be tamped down by all of these these interventions which might explain the functional improvements that we see uh from from using these interventions in age mice”

“so the rationale there uh is both based on the human data which again is limited right but we've talked about the the daily versus uh weekly dosing for immune function and again we've also talked about why i think that readouts of immune function are probably telling us about the underlying inflammatory state which i think is a big part of what rapamycin is doing so so that is suggestive that daily dose weekly dosing is at least as good as daily dosing and it's also suggestive that weekly dosing has fewer side effects”

“and i think there's a ton of evidence that that many of the benefits that we see in mice from rapamycin occur because it tamps down on that sort of sterile inflammation that goes along with aging right the inappropriate activation of the immune system”

“so i think that again a lot of these age-related conditions that are inflammatory driven you can kind of reset that with an eight-week treatment and and rap mice and i suspects analytics if we had goods analytics would do pretty much the same thing”

“just from a very simplistic conceptual perspective you could imagine that that one of the things rapy is potently doing is knocking down this hyperactivation and this is something I wanted to mention but but but we didn't talk about in both the manic study and the pangang study the vaccine was given after the transient treatment with rapamycin was stopped”

“I have very much in in the last five to 10 years shifted my thinking particularly in the context of people and probably in other mammals towards the anti-inflammatory effects and particularly the ability of rap ay to knock down sterile inflammation in in the context of an aged animal that seems to me to that a lot of the the benefits that we see in terms of organ and tissue function can be plausibly traced back to that effect of Romy”

“I think that's one of the major things certainly um you know that there's good evidence for enhancement of autophagy. There's good evidence for changes in protein translation and those things are not mutually exclusive to inflammatory changes anyway.”

“And I think if rapamy is girotective and um when I say if I mean in humans, I think it's unambiguously protective across most species, but we still don't know if the species of interest is is is going to benefit from this drug. And we may never by the way, but it's probably working by tamping down the chronic inflammatory component of what we see with mTor activation, which by the way might actually involve inflammation as well as one of the many things.”