August 17th, 2024
We're getting fairly near to the end of the study - but how near, we certainly can't yet say. Six of the 20 treatment groups, two male and four female, are now extinct, but the all-treatment groups of both sexes are still at 25% survival at over 35 months of age, which gives hope that the longest-lived mouse in the entire study will turn out to be fairly impressive. Across all 20 groups combined, 67 mice are still alive.
The more detailed analysis, teasing out the relative impact of different treatments, is getting more and more clear and interesting. Here are a few highlights.
I think we have to accept that our senolytic was a bust. We have some theories about why - more on that in due course - but in short we definitely do NOT think senolytics in general are useless, just that there's still some way to go to extract their full potential.
As I noted in the last update, the impact of the other damage-repair treatments (HSCs and telomerase) over and above rapamycin is disappointingly insignificant in females but looks rather good in males. In fact, at this point it begins to be arguable that the damage-repair treatments actually DIMINISH the benefits of rapa in females - but have the opposite, i.e. beneficial, impact in males. This is definitely something requiring more thought - and, of course, more studies - but first let's see how things look when RMR1 is complete.
The only-telomerase group is the one with the starkest sex-disparity: bucking the above trend, it was downright bad for male mice but definitely beneficial for females. Was that disparity big enough to survive statistical significance, given how many hypotheses we are testing simultaneously in this study? Watch this space!
In that vein, I must as usual repeat my caution not to run too much with any of this quite yet. Nothing that I say above has been validated by rigorous statistical analysis, and the main reason it hasn't is that there is still so much that can change as a result of those last 67 mice. If you doubt me, just look at the all-but-rapa males over the past 250 days.
In the first 125 of those days, there were 15 deaths, reducing the cohort from 19 to 4 (not including those culled for tissues); and in the subsequent 125 days, there have been... zero deaths. We can expect more such fluctuations - it's an inevitable consequence of the fact that this experiment started with "only" 1000 mice, not 10000.