mice
Article
mice is a recurring concept in the Astral Codex Ten archive, appearing 3 times across 3 issues between December 02, 2021 and September 09, 2024. The archive places it in contexts such as “A well-regarded research center ran a big study on nicotinamides in mice and found that they lived no longer than usual”; “in animal studies, mice without the FAAH gene did seem to experience less pain (not zero) than control mice”; “This technology already works in mice”. It most often appears alongside Harvard, @the_megabase, A Pan-Species Welfare State.
Metadata
- Category: Concepts
- Mention count: 3
- Issue count: 3
- First seen: December 02, 2021
- Last seen: September 09, 2024
Appears In
Related Pages
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- Harvard (2 shared issues)
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- @the_megabase (1 shared issues)
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- A Pan-Species Welfare State (1 shared issues)
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- ACX Grantees (1 shared issues)
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- ACX MEETUP (1 shared issues)
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- Alexandre Gueniot (1 shared issues)
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- Algernon’s Law (1 shared issues)
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- Alzheimers (1 shared issues)
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- Apimostinel (1 shared issues)
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- Aristotelian virtue theory (1 shared issues)
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- Astralcodexten Com (1 shared issues)
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- Australia (1 shared issues)
External Links
Source Context
Recovered passages from the original issue text. When the raw archive preserved outbound links inside the source passage, they are listed directly under the quote.
If you want to live longer, can you just add more sirtuins? These people say they gave mice a gene that caused them to overproduce sirtuins, and the mice lived 30% longer. Other people have tried the same experiment in worms, fruit flies, etc, with controversial but generally positive results.
Inline links: These people say, controversial
Suppose you’re not a mouse, can’t get genetically engineered, and you have a normal aversion to diet and exercise. Is there a pill you can take? Yes! A suitably foreboding one, even! Rapamycin gets its name from Rapa Nui aka Easter Island, where it was discovered in a fungus living beneath one of the giant stone heads. It’s a strong inhibitor of mTOR (in fact, the “TOR” in mTOR’s name stands for “Target Of Rapamycin”). Mice on rapamycin live about 10% longer than usual. Can you take rapamycin? Probably a bad idea, it’s a potent immunosuppressant. Organ recipients take it sometime to quiet their immune system down to the point where it stops rejecting the transplant, but it’s not a lot of fun.
Inline links: live about 10% longer than usual
That doesn’t mean we can’t be immortal, though. Sinclair’s lab has another research program, focusing on stem cells. These produce new, epigenetically healthy cells wherever they’re placed. And we now know that with a couple of chemicals called Yamanaka factors, you can make adult cells become stem cells again. Sinclair’s idea is to genetically engineer triggerable Yamanaka factors into the cells of human adults. Then, when you’re starting to feel old, you trigger the factors, some of your cells revert to stem cells, and they replace your old decaying cells with epigenetically healthy ones. Every biologist I mention this to has the same objection, which is “won’t that make you have every kind of cancer at once?”, and, in their defense, the first hundred times Sinclair tried this his mice got some pretty crazy cancers. But he swears they have solved this problem and the mice are doing fine now. Some of them are living about 40% longer than normal, which I notice still isn’t immortal but seems like a step in the right direction.
Marcin said he’s pretty concerned about this. He thinks there’s some supplementary evidence that FAAH-OUT is involved - in animal studies, mice without the FAAH gene did seem to experience less pain (not zero) than control mice, and mice given FAAH inhibitors showed less anxiety. He’s currently talking to the University College London team that did the original Cameron studies to see what they think of this, and whether they have any good explanation. If UCL eventually decides they messed up, Marcin has some backup low-suffering genotypes he can use instead, and is willing to look for more - hopefully not the ones that lose the sense of smell or the ability to sweat.
Inline links: mice without the FAAH gene, mice given FAAH inhibitors
I can’t find anyone claiming to know exactly what went wrong with BIA 10-2474 (see here for what we do know). But the FDA released a statement a few months later saying they were confident that it was a particular feature of BIA 10-2474 and not a problem with FAAH inhibition in general. I don’t know their exact reasoning, but it might have to do with many other pharma companies trying different FAAH inhibitors with no problem. Far Out adds that the FAAH knockout mice also seem to do fine.
Inline links: see here for what we do know, the FDA released a statement
1: ACX commenter Metacelsus is a Harvard bio PhD who the excellent De Novo blog; he also reviews most ACX posts and grants on biology for me. He recently co-founded a startup, Ovelle, to commercialize his academic work on gametogenesis (turning arbitrary cells into eggs). If this worked, it could replace the complicated and invasive egg harvesting process of IVF with a simple blood draw or mouth swab. But beyond that, it would allow women to circumvent menopause by creating eggs at any age (women can safety become pregnant well into their 50s, they just lose the ability to create eggs naturally), and maybe (this is still speculative) allow gay couples to have biological children. And with a couple of extra steps, you could turn this into a supercharged version of embryo selection that could essentially end all genetic disease (existing techniques don’t give you enough rerolls for more than incremental gains). This technology already works in mice, and some companies (including one backed by Sam Altman) are working on translating it to humans - but IIUC Metacelsus is coming from an academic lab that’s gotten significantly further. Ovelle is looking for people who want to invest or work for them (remember, investing in biotech is a minefield best left to professionals, and working in biotech is terrible and soul-sucking). You can contact them here.