December 22nd, 2023

Here's RMR1 update #10, just in time for Christmas 🙂

I don't have anything big to report this time other than updated survival curves, so let me instead start by highlighting that we have now posted a description of RMR2, the second in this series of mega-studies. Please peruse it and consider contributing to LEVF so that we can start it soon!

Meanwhile, I think a couple of comments are in order concerning the survival curves. The first is the perennial one: PLEASE PLEASE don't infer anything AT ALL from them with any significant level of confidence. EVERYTHING at this point is totally tentative.

But with that said... first let's look at the females. Remember that the ten treatment groups were split across four cohorts, so the curves end at different places; essentially that means you should really only be interested in where the curves are at age 835 days.

The remarkable fact is that the four treatments are currently coming out as almost exactly additive: the no-treatment controls are doing the worst, the all-treatment group is doing the best, and all four three-treatment groups are doing better than any of the one-treatment groups, with the sole exception that the "only rapamycin" group is outliving a couple of the three-treatment groups.

Accordingly, the main thing to note is the magnitude of the benefit being conferred, which is really remarkable: the all-treatments group has the same survival at 835 days that the no-treatment group had at 690 days. And the study only began at 580 days!

So at that survival level, namely 80%, we're more than achieving the RMR goal of doubling remaining lifespan starting from treatment initiation.

It's broadly the same story with the males, but somewhat less clearly. First, you may be surprised that fewer males have died thus far than females - aren't females supposed to live longer? Well, no, it happens that the strain we're using, C57Bl/6, is well documented to have a longer male than female lifespan.

OK, so the weird aspect that screams out is that the two groups that are doing the worst are three-treatment groups! Huh? But if we set aside those groups for a moment, the pattern does resemble the females. Again the all-treatment group is doing the best and the no-treatment group the worst, and the two remaining three-treatment groups are outperforming all four one-treatment groups. Also, the magnitude of benefit is similar to the females.

As noted, I refuse to infer anything at this stage about why the no-HSC and no-rapa groups are doing so badly.

The final thing to say is that, for both females and males, the only-rapa group is doing the best out of all the one-treatment groups, and the no-rapa group is dong the worst or second-worst out of all the three-treatment groups. This can be viewed as one more justification of our decision to give rapamycin to all 1000 mice in RMR2.