February 26th, 2023

Here's the first update on the "Robust Mouse Rejuvenation" study that LEVF is funding at Ichor Life Sciences in Syracuse.

Well, actually it's not so much an update as a kickoff announcement. We've planned this immensely complex study in such a way that we could begin it as soon as all the prerequisites (including masses of custom reagents) were in hand, subject to an age at onset no younger than 18 months, but knowing that any age up to 20 months would be fine. In the end we are starting at 19 months, which for the 200 oldest mice (see more below on our cohorts) was TODAY! You may wonder whether mice have been dying on us before the experiment begins: the answer is, yes a few, but only VERY few, and we bought enough extras to be able to compensate.

Right, cohorts. We recognised from the outset that there would be value in staggering our various treatment groups, so as to avoid spikes in how much manpower would be needed on a given day or week - plus, it turned out that Jackson Labs, who supplied our mice, also found it easiest to provide mice with a range of birth dates. So we bought mice in four groups (cohorts), each with a birthday range of only a day or two, but with groups spaced by intervals of two weeks. We also wanted to have each of the ten treatment groups be entirely within one cohort, so these ended up being split not as four groups of 250 mice but as 200, 300, 200 and 300. So the first 200 mice are 19 months old today (+/- a day or so), the next 300 will reach 19 months of age on March 11th, the next 200 on March 25th, and the last 300 on April 8th.

The first cohort, whose treatment starts today, will have relatively simple treatment regimens. These 200 mice will constitute treatment groups 1 and 2, which means that half of them, i.e. 50 males and 50 females, will comprise the "all controls" group, and the other half the "only rapamycin" group. Both of these groups will actually be further split in two, with 25 of each sex receiving "mock" control treatments and the other 25 receiving "naive" controls. What distinguishes the two? Well, "mock" means we do everything to the mice that we would if they were getting the intervention, except that we don't actually give the intervention itself, whereas "naive" means we do nothing.

The purpose of this is to be able to factor out any impact on lifespan or healthspan that the delivery mechanism may have. So, for example: we are administering rapamycin in the mice's food, but we are doing it in a particular way that has worked well for other groups, namely encased in microcapsules. So, half of the mice that are NOT getting rapamycin will just get regular food, but the other half will get food containing empty microcapsules. Similarly, our telomerase gene therapy will be delivered virally, so among the mice that are not getting telomerase (which includes all 200 of the mice whose journey begins today), half will receive no virus, and half will get virus without telomerase.

And I said "relatively simple", right? For any of you who didn't hitherto appreciate why this is a study on a whole new level from what anyone has done in the past, I hope I'm fixing that. Cohort 2, which will include our first multi-intervention group, will indeed be another level up from what I've just outlined... look out for my next update.

I was also slightly oversimplifying when I said the experiment starts today, because really it's been going for a few days already. That's because we've been gathering baseline data on cohort 1, in advance of the administration of any intervention. Baseline information is of all the same types that we'll be gathering during the study, which are described on the main project page.

So, here we go! Future updates for the next six weeks or so will be rather like this one, giving in-depth descriptions of what these interventions actually consist of in practical terms, as the subsequent cohorts enter the experiment. Thereafter, all the mice will be under intervention and the updates will transition to descriptions of the latest data - including survival curves, of course, but also as much data on biological age and health as we have at any point.

That's all for now. Let me close by heaping wholly inadequate praise on the incredible people who are making this happen. My main scientist Caitlin is currently in Syracuse complementing the efforts of the Ichor team; the Ichor CEO, Kelsey Moody, and veterinarian, Danique Wortel, are continuing the absolutely heroic effort they have applied to this project for the past several months as it has taken shape; and every bit as importantly the many Ichor staff, spanning all manner of areas of expertise, are and will be there on the ground doing all the myriad things that this unprecedentedly ambitious study entails. I've said this before and I'll be saying it again, a lot: this is far and away the most important and ground-breaking experiment I've ever led. It's a humbling privilege to be coordinating such an amazing group.

Which brings me to the people who MOST fundamentally made this study happen: the donors. This study is costing about $3M, without which it would have remained merely a twinkle in LEVF's collective eye. Now that our research has reached the point of testing interventions in mice, rather than in cell culture which has dominated my focus hitherto, our progress depends more than ever on donor generosity. Thank you all so, so much.

Cheers, Aubrey