Abelard Lindsay

I am the creator of the CILTEP stack. Software engineering. Medical research. Transhumanism. Making people smarter by designing better nootropics.

[Abelard Lindsay @ciltep]

@drmichaellevin @kanair I think people arguing about consciousness are like Romans looking at lightning and thinking it's evidence of flammable liquid in the sky. There's some basic science about it we don't understand yet and might not for some time.

[Abelard Lindsay @ciltep]

@bryan_johnson Lol, the moon? You can't hide anywhere from drones and global satellite surveillance. Might as well lean into the future.

[Aging Research News @AGE]

Urolithin A: Potential to enhance autophagic clearance and mitigate neuroinflammation in Alzheimer’s disease
https://t.co/qN6v04Dq6o

[Abelard Lindsay @ciltep]

@is_OwenLewis It's a shame carbon nanotubes are so toxic.

[Abelard Lindsay @ciltep]

@fedichev Aging may also be a programmed stage of development like puberty. For example, people with the disease progeria age much faster than normal, but also go through early puberty. If aging was just accumulated damage, puberty would not also arrive early in these pathologies.

[Aakash Gupta @aakashgupta]

Spouses of Alzheimer's patients are 6 times more likely to develop Alzheimer's themselves. They share daily saliva exchange for decades. Their oral bacteria converges to the same strains.

In 2019 Cortexyme published a paper in Science Advances showing Porphyromonas gingivalis, the bacterium behind gum disease, was present in over 90% of postmortem Alzheimer's brains. They also found its DNA in the cerebrospinal fluid of living Alzheimer's patients.

P. gingivalis is the keystone pathogen of periodontitis. The CDC says 47% of American adults over 30 have periodontitis right now.

The mechanism is specific. P. gingivalis produces enzymes called gingipains. Two types: one cuts proteins at lysine residues, the other at arginine. Tau, the protein that holds your neuronal scaffolding together, is loaded with both amino acids. In cell culture, gingipains shred soluble tau within one hour of infection. The fragments seed the paired helical filaments that become tangles. Tangles are Alzheimer's.

Mice fed P. gingivalis through the mouth grew amyloid plaques in their brains. Hippocampal neurons died. The bacteria crossed the blood-brain barrier and started chewing through the same proteins that fail in human Alzheimer's patients.

Cortexyme built a drug called atuzaginstat to block gingipains. Phase 1 was clean. They ran a 643-patient Phase 2/3 trial called GAIN.

The FDA hit it with a partial clinical hold for liver toxicity. The drug missed both primary endpoints. In August 2022 Cortexyme shut the program down, renamed itself Quince, and pivoted to bone disease.

The subgroup with the highest baseline P. gingivalis loads still showed cognitive improvement on secondary endpoints. The bacteria itself kept showing up in postmortem brains across independent studies after the trial closed.

Periodontal disease shows up 10 to 20 years before cognitive symptoms in people who later develop Alzheimer's. By the time someone forgets a name, the bacteria has been working for two decades.

The intervention point is upstream of your skull.

[Abelard Lindsay @ciltep]

@bryan_johnson Immune sensesense again shows up as the universal lifespan limiter.

[Abelard Lindsay @ciltep]

IMHO, The four pathways are probably keap1/nrf2, htrt, ampk/mtor, alk5/oxytocin. Probably inhibiting fibrotic growth is important like IL inhibitors too.

[John Cumbers @johncumbers]

David Sinclair's lab may have just found the $100 pill that reverses aging.

Over the holidays, his team ran what he calls a "hail mary experiment."

They gave old mice a "longevity" cocktail three times a week for 4 weeks.

He didn't reveal what's in it - only that it contained molecules that work on the four longevity pathways that control the epigenome.

They weren't expecting any significant results.

Yet every treated mice came back physiologically younger while the controls didn't.

Biological age clocks confirmed the reversal.

This changes the trajectory for longevity medicine.

The gene therapy his company is taking into human trials costs over $10 million to manufacture per batch.

It requires a direct injection into the target organ.

These oral molecules cost roughly $100 for a month's course.

If they're able to put these molecules into a pill that patients can take instead of them using a multi-million dollar gene therapy, they'd save a ton of money.

"Imagine in 10 years you just take a pill for 4 weeks and you get younger. That's what we're headed towards. I can see how this is going to happen."

The proof of concept exists in animals.

Now it's a race to get it into humans.

— David Sinclair (@davidasinclair) on Peter Diamandis' (@PeterDiamandis) Moonshots podcast

PS. David Sinclair is speaking at SynBioBeta on May 6th this year, discussing the science of slowing and reversing aging.

If longevity is the world you're in, the investors, partners, and scientists shaping this space will be in the room.

You won't want to miss it:

https://t.co/xK8pNt7tLM

[Abelard Lindsay @ciltep]

@techno0ptimist Rutaecarpine pills claim they can help the body speed up the breakdown of caffeine. https://t.co/KpYj4K1Wh4

[Niklas Anzinger 📍 Infinita @NiklasAnzinger]

He was diagnosed with rare bone cancer.

He exhausted the standard of care: surgery, radiation, chemotherapy.

There were no viable trials for his case. No approved treatments. No doctor willing to promise any potential for hope.

That’s where most journeys end.

Not his.

[Abelard Lindsay @ciltep]

@techno0ptimist Write 500 words every day, even if it's garbage. Just doing it badly will help you get better. You can get AI to confidentially criticize your writing if you're sensitive about it.

[Abelard Lindsay @ciltep]

Study says BDNF is upregulated in older people with exceptional memory.

https://t.co/RuDytmOqu6

[Abelard Lindsay @ciltep]

@bryan_johnson Hey go watch "A Scanner Darkly" if you want to see what it's like when a person's brain becomes so neuroplastic that it decides to believe just about any random thought that comes to mind.

[Abelard Lindsay @ciltep]

@KiesowPaul @wings1673 The tyramine issue is very overblown. From what I remember arguing about this on Longecity forum back in the day, there were only a few case reports.

[Abelard Lindsay @ciltep]

@bryan_johnson Bryan, please do not mess with your GABA or Opioid receptors with any synthetic agonists. I want to read more interesting content from you than how to do drug tapers without severe withdrawal symptoms.

[Abelard Lindsay @ciltep]

@techno0ptimist This has a 1990s System 7 Mac OS vibe.

[Abelard Lindsay @ciltep]

@techno0ptimist You ever see the movie Pi? https://t.co/hsAy6IAlO5

[Liz Parrish MBA @ParrishLiz]

Known as cyclin D-binding myb-like transcription factor 1 or DMTF1, the scientists found that this protein's levels are repressed in the “aged” neural stem cells and that restoring it is sufficient to restore the regeneration capabilities of such neural stem cells.
https://t.co/cdM5oICbNH

[Abelard Lindsay @ciltep]

@BrianRoemmele Alk5 inhibitors are not the safest drugs. None are approved, and in clinical trials they caused heart abnormalities when not carefully dosed. https://t.co/FzvsKjGGQA

[Brian Roemmele @BrianRoemmele]

The 70% Life Extension Nobody Is Talking About

Two cheap drugs. One university lab. A 73% increase in remaining lifespan for elderly mice. The longevity breakthrough that should be front-page news and why decentralized science may be the only force that can bring it to your medicine cabinet.

Oxytocin and Inhibitor Extend Mouse Lifespan

Combining oxytocin and Alk5 inhibitor extended elderly mouse lifespan by 73%. Inexpensive drugs, no gene therapy. Major longevity paper.

Why Important: Demonstrates affordable pharmacological approaches to longevity, bridging natural hormones with targeted inhibition for human applications.

https://t.co/NXmQXVCZdP