All of InquilineKea's Comments + Replies

https://twitter.com/alexeyguzey/status/1728549209949995299

Semaglutide would save more animal lives than doubling the percent of vegetarians (and I have sources)

Brain organoids are a way to quickly get functional/morphological significance readouts of intelligence-related genes (or genes related to other functions), so they are useful as a way of studying intelligence.

https://www.frontiersin.org/journals/science/articles/10.3389/fsci.2023.1148127/full

As a huge, huge moonshot, one could investigate avian brain organoids as an alternative substrate for intelligence (they are way more space-efficient than mammalian brains, and potentially could do way more compute in a small (manageable) volume if appropriately cultu... (read more)

As N=1, I became vegetarian in 7th grade. Extreme levels of disgust-sensitivity [PETA is good at this] fueled this decision and I feel like I want to puke if I taste meat (I suspect disgust-sensitivity isn't as big of a factor in utilitarian EAs who go veg*)...

The factors were:

• personal interactions with chickens I had when staying over at a Woodinville farm (and then personal interactions with a Bellevue Chinese restaurant where I felt angered at how insensitive people were killing the aquarium fish right on site just for dishes (I was seeing murder at sit

https://slatestarcodex.com/2019/12/11/acc-is-eating-meat-a-net-harm/?utm_source=substack&utm_medium=email

(a good number of people feel just as fine on a vegan diet as a non-vegan one [example] - most of the potential "costs" are in terms of energy/vitality which they will feel if they feel it). I am ovo-vegetarian and I have reasonably high iron levels myself. From the limited studies available, vegans have lower ACM than even vegetarians do.

It's important for people to get an ION Panel to test for amino acid deficiencies (these are hard to order w/o a... (read more)

There are many neurofeedback clinics and companies like Peak Brain Institute (they track brain waves and some people report drastic benefits, esp w/cognitive control, in response). The studies could be higher-quality and attract a broader range of people. They could also be way more widespread (also see what Neurable/Neurosity are doing). I tried neurofeedback once and can certify that I did feel very differently afterwards (in a good way!) but these protocol are usually very expensive (near-term AGI makes this matter way less). Many neurofeedback protocol... (read more)

FYI for the Caesar's $1500 bonus bet..

"f) Bet Credit stake is not included in any winnings from a redeemed Bet Credit."

I bet on the Rockies winning against the Padres (they were an underdog) and I only got $2430 out of $1500 invested. If I had used that bet credit on an overdog that won, I would have lost money on net. [this is different for some of the other sites]

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Also you HAVE to get the FIRST DEPOSIT right on DraftKings - I wrecked my first bet there by depositing only $25 and then placing a microbet just because I was scared... (I should have place... (read more)

For most people, it's better to use https://www.caichinger.com/blog/2018/04/19/kelly_criterion4/ than expected value

Does the Bonus Bet token for DraftKings only apply for the first wager you put money for? (it's "up to $5000", but if you bet for less than $5000 [eg only make a deposit of $500], are you not filled in for 5,000 ever?)

https://www.science.org/doi/10.1126/science.add9330?utm_campaign=SciMag&utm_source=Twitter&utm_medium=ownedSocial just came out!

Also microplastics/nanoplastics too

https://forum.longevitybase.org/t/how-to-reduce-microplastics/126/16

https://waterpurificationguide.com/water-filters-that-remove-microplastics/

The smallest can get through the blood brain barrier and they are this generation's air pollution

Also how does one stress-test tendency to reveal infohazards when one is under severe stress, like anger, despair, desperation, or mania?

Ideally one would stress-test as little as possible..

Does pretending that one isn't employed by X (one can have plausible deniability when one says that "one is employed by a stealth AI organization" - and there are enough stealth AI organizations out there that one can pretend to be employed by any of them), when one is in fact employed by X, help reduce the temptation to spread infohazards? (in which case - if someone is secretly employed by institution X but does not want to say that they're employed by X, how would they pretend not to be a NEET so they wouldn't face the social stigma associated with bein... (read more)

How does one translate mathematical/high-level agenty-foundations guidelines into code/instructions that an RL agent (or any AI agent, including a scaling laws one) can follow?

Has anyone noticed that nightmares are also associated with "bad trips" from psychedelics, given that psychedelics are "waking dreams"? (the fear of a bad trip is what interferes with many of the profoundly beneficial effects of psychedelics transpiring to a broader population => significantly blunts their "healing potential")

Just out of curiosity - how much time is wasted on evaluating half-ass'ed proposals?

>People are often grateful to you for granting them money. This is a mistake.

Sometimes they're resentful if you reject them (though this depends on community and is probably highly asymmetric).

At what point can large language models start to do distillation, especially of the early LW sequences?

My list: https://www.quora.com/If-there-was-somebody-you-wanted-to-know-better-what-one-question-would-you-ask-of-them/answer/Alex-K-Chen

Also hi Akash!!! Nice to see you here!! :) Jeffrey Yun pointed me here! :)

more on mosaicism - https://twitter.com/jpsenescence/status/1084560766735450113

João Pedro Magalhães

The large number of mutations with age recent studies are finding in some human tissues showcase how difficult it will be to significantly intervene in aging because we can't easily get rid of mutant cells and replace them by pristine cells.

https://www.nature.com/articles/d41586-018-07737-8 is very deep too - actually it hints that many older cells are dominated by pro-growth/pro-survival mutations that don't complete all the necessary conditions for ca... (read more)

It's not just tau/junk that contributes to cytoskeleton damage - the cytoskeleton is made of proteins that are easily oxidizeable in the same way that nuclear pore complexes are, and damage to NPCs don't have tau as their primary culprit.

On moral progress - I think it's highly plausible that future generations will not be okay with people dying due to natural causes in the same way that they're not okay with people dying from cancer or infectious diseases.

Too much tau junk → too much cytoskeleton damage

That's not the only thing that causes cytoskeleton damage.

Ultimately one path forward is: how do you create the data-set/papers that can be used by a new version of GPT-3 to suggest potential interventions for aging. That's why ALL of the creative new technologies people use to treat genetic diseases or cancer (along with nanotechnology - yes UPenn people are already creating nanobots) can help, even if not originally designed for aging.

Cytoskeleton damage can be upstream/causal if it affects lysosomal positioning (just as anything that affects autophagy reaching the sites it needs to reach can be upstream/causal). It also affects cellular stiffness, which then affects whether molecules reach the places they should be reaching.

Lipofuscin can also be a secondary kind of damage too, and it doesn't seem to adversely affect the cell too much until its concentration reaches a critical level. 

Much of SENS was developed before the massive bioscience advances in understanding over the last 1... (read more)

This would only matter a lot if you want to disentangle what metabolism is doing (which is vast) and try to get it to do the impossible: prevent every single lipid and protein from going bad. I doubt even an AI god could make that happen, nevermind mere mortals equipped with what amount to fancy expert systems.

Preventing every single lipid and protein from going bad is precisely a problem that "AI" could help solve - one could envision artificially designed enzymes that can get into the cell and specifically modify every unnecessary oxidative modification.... (read more)

Yes, damage to long-lived NPCs can be causative given that mislocalized nucleocytoplasmic transport can be causative in reduced autophagy with age. From Autophagy in aging and longevity

immpaired nucleocytoplasmic transport and loss of nuclear integrity may derail autophagy
The proper nucleocytoplasmic transport of autophagy-inducing TFs such as TFEB by RanGTP-dependent importins and exportins and the retention of such factors in the nucleus are important processes in proper autophagic regulation. In fact, nuclear pore complexes (NPCs), w

Do you have evidence that this may be a cause of normal human aging rather than of progeria and aging in worms?

https://www.sciencedirect.com/science/article/abs/pii/S1566312408600528

The cytoskeleton is how the neuron is able to transport mitochondria, proteins, lysosomes,  and other organelles where they're supposed to be. Disruptions in axonal transport that happen due to cytoskeletal damage prevent the neuron from being able to transport cargo to the right places, especially to synapses). Dendritic size (and "stubs") often shrink wrt age in pa... (read more)

It's way easier just to clear them out...

Um no, it's much easier to fix oxidative modifications before they all irreversibly clump together into weird aggregates that become inaccessible to most enzymes. See figure at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536880/bin/gr1.jpg . Early intervention >> late intervention. "The reduction of lipofuscin/ceroid formation by pharmacologically decreasing oxidative stress may represent a more promising approach to the problem. "

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536880/

Again, better tools

Isn't there a difference between creating entirely new frameworks, and just adopting frameworks to different species in parallel?

For instance, it seems that adopting frameworks to different species in parallel often ends up happening over time (as we've seen people gradually adopt cognitive ethology from chimpanzees and captive dolphins into wild dolphins, elephants, african grey parrots, kea [where academic labs do exist to study them], capuchin monkeys, and new Caledonian Crows). It seems that some species of animals are intensively studied, and the vast... (read more)

SENS also doesn't mention cytoskeletal aging (eg https://www.molbiolcell.org/doi/10.1091/mbc.E18-06-0362 ). It's important because cytoskeletal proteins are among the most abundant proteins and are not easily replaceable or degradeable, given that they're often long-lived and you can't cut them in half without disrupting the rest of the cell [1]. You might call it a "more general version" of damage to elastin.

[1] this is also true for the most general case including structural proteins like lamin - aberrant transcripts of lamin also accumulate during aging... (read more)

More than anything, the main limitation of SENS is that it doesn't even plan for future interventions that are guided by AI/ML. Many of the smartest people I know (esp the computer scientists), for better or worse, think that a cure for aging will most likely come through AI, but they aren't able to describe/specify how this happens - they'll just magically think it will be. And most people in SENS don't even plan on how to make the kinds of experimental design that will make it easier for experiments to produce vast amounts of machine-readable output that... (read more)

As for other forms of damage, it does seem that SENS focuses on repairing damage when it has already accumulated, rather than investigations into targeted interventions that can significantly slow this damage. Eg with proteasomes. The quote below is quite powerful~~

Fortunately much of the accumulated damage can be removed and the damaged proteins can be degraded and replaced by non-damaged ones. In fact, a mild degree of modification or damage to a protein makes it a better candidate for degradation by the 20S Proteasome or other proteases [33, 39, 41, 51]

Actually, the most important limiting factor is the funding of the right research. There's just no way around that regardless of how good tools become.

Lol, everyone in the SENS program tells people"GIVE US MORE MONEY AND MAGICAL THINGS WILL HAPPEN", but like, this seems to make other people feel like they can't contribute to changing the mission of SENS, given that it seems to delegate all control to whoever controls SENS. I know SENS creates mission reports and such, but so far they still haven't been great at convincing most HNWIs that SENS has made any ... (read more)

No aging enables autocrats to stay in power indefinitely, as it is often the uncertainty of their death that leads to the failure of their regimes. Given that billions worldwide currently live under autocratic or authoritarian governments, this is a very real concern.

Among the largest nations that are most relevant to the world (or have a disproportionate ability to shape what happens to the world relative to their ability to be shaped by other countries), it only applies for China and Russia, and it's unclear whether Xi or Putin strongly care about immort... (read more)

As I wrote here, I think this could be due (in part) to biases accumulated by being in a field (and being alive) longer, not necessarily (just) brain aging. I'd guess that more neuroplasticity or neurogenesis is better than less, but I don't think it's the whole problem. You'd need people to lose strong connections, to "forget" more often.

George Church is over 60 and I've heard some people refer to him as a "child", given that he seems to not strongly identify with strongly held beliefs or connections (he's also not especially attached to a certain identit... (read more)

Besides the cancer thing, SENS ignores telomere attrition, because it's still unclear if telomere attrition is a significant cause of aging. And the likelihood that WILT will be needed is still above 50%.

Isn't early detection of cancer (and intervention) more feasible? 

Also haven't you heard of the use of lasers to disrupt/destroy amyloid plaque? (which could presunmably also be useful for protein aggregates?)

#ALLTIMEIMPORTANTTHREADS #IMPORTANTTHREADS #INFLECTIONPOINTS #ALLTIMEMOSTIMPORTANTPOSTS #YOUWILLREGRETNOTINCORPORATINGMOREOFTHIS #ALLTIMEFAVORITEANSWERSOFAKC

But there's still some controversy about whether genetic mosaicism really leads to any age-related disease or condition, and that's why SENS doesn't target that particular form of damage yet. DNA damage in the nucleus can cause cancer and cell senescence and is targeted by OncoSENS and ApoptoSENS respectively

https://www.nature.com/articles/s42255-020-00304-4

Genetic mosaicism, in itself, isn't nec... (read more)

This is a great overview post of SENS, and I've read a lot. 

FWIW, both SENS and Hallmarks neglect the mentioning of A LOT of other kinds of damage but which are mentioned in Jan Vijg's book (eg genetic mosaicism, improper stoichiometric ratio of synthesized proteins, histone loss, proteins and DNA not being localized in places they should be localized, accumulation of extracellular metabolites that get trapped in the cell and don't get extruded out). SENS has many of the right high-level initial ideas regarding how to repair damage (it helps train peo... (read more)

Shouldn't we weigh neurons by level of graph/central complexity? (eg neurons by how "central" they are to the system). Many neurons simply don't factor into evaluations of hedons (even motor and sensory neurons)

Play behavior is in general not found in birds, with the exception of the highly intelligent corvid family

You forgot kea and cockatoo parrots. https://www.abc.net.au/news/2020-12-26/birds-that-play-are-smarter-finds-gisela-kaplan-research/12990902

Also, possibly emu (https://www.buzzfeed.com/annamenta/you-go-emu-you-play-fetch), which have among the largest brains in the bird world.

A lot of hallmarks (eg genetic mosaicism or improper stoichiometry or proteins not doing what they're "supposed to do") are systems effects rather than effects that can be analyzed reductionistically. Fedichev and Gladyshev have lots of papers that hint in that direction

While old generation dying is one way of getting scientific and intellectual change to be enacted, there are longer-term trends towards reduced gatekeeping that may reduce the cost of training (eg when people prove that they're scientifically competent WITHOUT having to go through the entire wasteful process of K12 + PhD), then this could inhibit the gatekeeper socialization effects of the old generation that prevent the new generation from feeling free to express itself w/o permission (programming, at the very least, is much less hierarchical because peop... (read more)

There also can be a significant difference between mere physical pain and actual suffering that leads to PTSD. It may be true mammals/birds can get traumatized, but few animals really reach the PTSD-levels of intense suffering (or lived resentment) that an elephant can experience after the death of all of its family members, or that an orca feels after its baby dies and it holds its young in its snout for days

[fwiw, elephants seem to be one of the only animals that becomes aware of persecution at a population-level - crows might be another example - these ... (read more)

There are some scientists who roamed around and never really crystallized (famous examples being Freeman Dyson and Francis Crick)

While old generation dying is one way of getting scientific and intellectual change to be enacted, there are longer-term trends towards reduced gatekeeping that may reduce the cost of training (eg when people prove that they're scientifically competent WITHOUT having to go through the entire wasteful process of K12 + PhD), then this could inhibit the gatekeeper socialization effects of the old generation that prevent the new generation from feeling free to express itself w/o permission (programming, at the very least, is much less hierarchical because peop... (read more)

https://smartairfilters.com/en/blog/is-air-pollution-affecting-your-productivity-in-the-office/

What makes for an ideal MIRI researcher? How would that differ from being an ideal person who works for DeepMind, or who does research as an academic? Do MIRI employees have special knowledge of the world that most AI researchers (e.g. Hinton, Schmidhuber) don't have? What about the other way around? Is it possible for a MIRI researcher to produce relevant work even if they don't fully understand all approaches to AI?

How does MIRI aim to cover all possible AI systems (those based on symbolic AI, connectionist AI, deep learning, and other AI systems/paradigms?)