--- Log opened Tue Aug 22 00:00:07 2023
--- Day changed Tue Aug 22 2023
00:00 < hprmbridge> nmz787> sup
00:02 < fenn> sup
00:02  * fenn slap chest
00:03 < hprmbridge> Eli> Dr. Stanfield is trying to do an actual human trial on rapamycin. The thinking is that if it's pulsed, it can extend lifespan without negative side effects. It's only theoretical. Nothing has really panned out for the life extension crowd except for exercise, diet, and sleep. Metformin turned out to be a bad move. GLP1 agonists have issues with lean muscle mass. We are still in the begging of
00:03 < hprmbridge> Eli> longevity research, but, I'm not super convinced about anything beating exercise, sleep, and diet. At best, you might just be trying to partially mimic those pathways in your body with exogenous substances. Hopefully I'll be totally wrong and there will be teleological reasons we can assume major life extension without gene editing embryos. Gonna have to go with kanzure on this one. We will see
00:03 < hprmbridge> Eli> what happens in the future.
00:06 < fenn> mimicking calorie restriction without actually needing to do it is a plus in my book
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00:07 < fenn> i think foundational science still needs to be done before any worthwhile interventions can be created
00:07 < fenn> stuff like "what is aging?"
00:08 < fenn> eli, we are all fighting against nature
00:15 < hprmbridge> Eli> The question is if we can mimic caloric restriction for a long period of time without negative side effects. My guess would be that there are optimal times for caloric restriction, and the best tactic would be to find out when those times are, and then recommend them to people. This sounds simple to say, but we don't have a lot of data on this. And, people really just want a magical pill that will
00:15 < hprmbridge> Eli> cure out negative phenotypes so they don't have to make any painful life choices
00:18 < hprmbridge> Eli> I can tell you what death is. The elimination of a gradient. Temperature, Pressure, and Ph returning to homeostasis with the environment outside the cell.
00:20 < hprmbridge> Eli> As we age, our homeostatic set point becomes more and more difficult to maintain. That's why a broken bone at age 9 is an inconvineince and at age 99 is a death sentence.
00:21 < hprmbridge> Eli> Most of the life extension treatments proposed are trying to maintain our homeostatic set point longer.
00:24 < fenn> right, robustness and the capacity for regeneration is probably more important than life span improvements
00:25 < fenn> i'm pretty sure the way to immortality will be through improving regeneration
00:25 < hprmbridge> Eli> Theres a doctor on youtube called Dr lustgarten who is doing a lot of self experimentation with blood work posted. Basically, he's working through all his biochemical pathways and using supplements one-by-one to see if he can improve all of his homeostatic markers of aging.
00:26 < fenn> good, we need more experimentation and more diversity of perspectives
00:26 < hprmbridge> Eli> He doesn't explicitly say that's what he's trying to do. But, effectively, that's what it is.
00:26 < fenn> i'm worried that most anti-aging researchers are chasing symptoms of aging
00:27 < hprmbridge> Eli> what do you mean?
00:28 < fenn> there could be a root cause of aging, which results in downstream effects, and those effects go on to cause yet more effects, until you have a whole spectrum of dysfunction
00:28 < fenn> or there could be multiple separate causes of aging working in parallel, and they just all happen to roughly correlate with chronological age
00:28 < fenn> how would we know the difference?
00:28 < hprmbridge> Eli> There have been a couple of papers trying to clarify all the causes of aging.
00:29 < fenn> do you see what you just did there?
00:29 < hprmbridge> Eli> One of the noteable one basically claims there are like 12 causes they can think of.
00:30 < hprmbridge> Eli> clearly, all of them are working in parallel. So, fixing one won't necessarily fix al the others. But, it could provide relief to individuals.
00:30 < fenn> why is it clear?
00:30 < fenn> why 12? why not 144?
00:31 < hprmbridge> Eli> it has grown from the original 8 or 9 in the first paper
00:31 < hprmbridge> Eli> https://www.sciencedirect.com/science/article/abs/pii/S0092867422013770
00:31 < fenn> "Hallmarks of aging: An expanding universe"
00:31 < hprmbridge> Eli> personally, I do like the biophysicist/systems biologist perspective
00:32 < fenn> this sure reads like a list of symptoms to me
00:32 < fenn> "We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis."
00:33 < fenn> maybe not stem cell exhaustion, but i'm not sure if i believe that is real
00:33 < hprmbridge> Eli> tbf, would it be possible to age if all of these things were "fixed"?
00:34 < fenn> games of whack a mole can go on indefinitely
00:34 < fenn> i wish there were a better metaphor
00:35 < hprmbridge> Eli> I think I understand what you mean. The devil is in "fixing" all these things
00:36 < hprmbridge> Eli> So this is the systems bio/biophysicist view of aging. And, I think it's really cool: https://pubmed.ncbi.nlm.nih.gov/18851981/
00:37 < hprmbridge> Eli> It could explain the difficulty in treating alzheimers, for example.
00:37 < fenn> "If a balloon is squeezed the air is moved, but does not disappear, instead moving into another area of less resistance."
00:38 < fenn> it's not a perfect metaphor because there is no mystical conservation of life force
00:39 < fenn> ideally we would be leveraging the body's own built in control systems to regulate everything, rather than clamping down on one variable or another and regulating everything externally
00:40 < hprmbridge> Eli> yup. that's why im big on exeercise, diet, and sleep.
00:40 < hprmbridge> Eli> we have to wonder if we can beat those three things or mimic them.
00:40 < fenn> great, but what are you doing in the channel if that's the final answer?
00:40 < fenn> exercise diet and sleep will get you to 90 or 100 if you're lucky
00:41 < hprmbridge> Eli> im trying to fund my own RCT
00:41 < fenn> see, i don't find much value in living 10% longer, unless it gets me to longevity escape velocity
00:42 < fenn> at the end of the century you're still dead
00:43 < hprmbridge> Eli> this might be fighting words in this channel, but I think longevity escape velocity is a pipe dream in our lifetime
00:43 < fenn> quite possibly so. there are many dead longevity researchers
00:43 < fenn> on the other hand, in the last 5 years or so we've seen billions of dollars poured into the field
00:44 < hprmbridge> Eli> I think getting average human lifespan to 100 years is reasonable. And something to aim for. Most of the improvements we've seen in longevity since 1900 have been due to lifestyle changes or changes in the environment.
00:44 < fenn> don't confuse maximum life span with life expectancy
00:44 < hprmbridge> Eli> We took lead out of water and gave people vaccines, ...
00:45 < hprmbridge> Eli> im not
00:45 < fenn> actually lead was greatly increased in the 20th century
00:45 < hprmbridge> Eli> would it be fair to say we took lead out of the environment?
00:45 < fenn> vaccines might be stealing credit from simply letting everyone have sanitation and sufficient protein
00:46 < fenn> not since 1900, no
00:46 < hprmbridge> Eli> right. Sanitation is change in environment. Sufficient protein is change in lifestyle. Youre agreeing with me
00:47 < hprmbridge> Eli> whats up with the papers saying we gained 10 IQ points due to lead reduction?
00:48 < fenn> https://cdn.vox-cdn.com/uploads/chorus_asset/file/4096558/lead_and_crime.0.png
00:48 < fenn> still searching for data from before 1930s
00:50 < fenn> the leaded gasoline research program was in mid-1920s
00:50 < hprmbridge> Eli> isn't your graph showing that lead levels declined?
00:52 < fenn> yes, since 1970
00:54 < fenn> it bothers me when people say "improvements to longevity" and then talk about life expectancy
00:54 < fenn> sometimes i wonder if it's willful
00:55 < hprmbridge> Eli> this is a good paper: https://www.sciencedirect.com/science/article/pii/S0002934316306003
00:57 < hprmbridge> Eli> ill try not to use them if it bothers you. but, I think the increase in number of humans living to historic records is probably correlated.
00:57 < hprmbridge> Eli> avg lifespan increase is probably correlated with life expectancy increase, I mean
00:58 < fenn> "Life expectancy, longevity, and maximum lifespan are not synonymous. Longevity refers to the relatively long lifespan of some members of a population. Maximum lifespan is the age at death for the longest-lived individual of a species"
00:59 < fenn> the actual definition of life expectancy is super technical but for our purposes we can pretend it's the average life span remaining
01:00 < fenn> obviously if you are shot by a bullet and die, it reduces your cohort's life expectancy, but you'd be stupid to claim that has anything to do with aging
01:01 < hprmbridge> Eli> right. would be an example of a change in environment affecting avg lifespan
01:02 < fenn> https://fivethirtyeight.com/wp-content/uploads/2015/05/goldenburg-oldest-person-chart1.png
01:02 < fenn> so apparently maximum lifespan IS still going up, but that's probably just because there are more people
01:02 < hprmbridge> Eli> and if you survived, the lead from the bullet would negatively affect your life which would be a change in "diet" 🙂
01:04 < hprmbridge> Eli> of course. There is going to be a correlation. And with the boomers aging, we can expect a major bump. These people who are extremely aged often have poor lifestyle choices, but still live a long time. It's likely genetic for these super agers
01:06 < fenn> or hormetic
01:06 < fenn> all those flavonols and booze and cigarette smoke might be turning on defense mechanisms that protect against aging
01:07 < fenn> (jean calment famously had lots of red wine and chocolate)
01:07 < hprmbridge> Eli> I think there is actually some preliminary evidence to suggest that the super agers actually do have freakish genetics. They are living old despite their lifestyles.
01:08 < hprmbridge> Eli> The latest book by Peter Attia goes into it a bit
01:10 < fenn> calment smoked occasionally until age 117
01:10 < hprmbridge> Eli> if you check out the wikis of some of the oldest people, they have lifestyles that would not be recommended by a doc
01:11 < fenn> wow ok a kilo of chocolate per week is a lot, and that's coming from a chocoholic
01:12 < hprmbridge> nmz787> where can you even play whack-a-mole for real anymore?
01:15 < fenn> pretty sure i saw it at the arcade
01:16 < fenn> https://files.sysers.com/cp/upload/editor/images/Human_Whackamole_3monkeys.jpg
01:17 < hprmbridge> Eli> ```Britain's oldest known First World War veteran thanked "cigarettes, whisky and wild, wild women" for his longevity as he was bestowed the freedom of his home town.```
01:17 < hprmbridge> Eli> https://web.archive.org/web/20070929095448/http://archive.theargus.co.uk/2006/4/22/210069.html
01:18 < fenn> hey i mean who are we to say he's wrong?
01:18 < fenn> i volunteer as test subject
01:18 < hprmbridge> Eli> #science
01:20 < fenn> calment had always been small
01:22 < fenn> wtf gerontology research group is gone?
01:23 < fenn> dying is bad for website uptime!
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02:00 < fenn> https://upload.wikimedia.org/wikipedia/commons/2/23/Ponce_de_Le%C3%B3n_in_Florida.jpg
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02:24 < fenn> "This page is related to longevity, which has been designated as a contentious topic."
02:24 < fenn> only on wikipedia
02:53 < fenn> green beans are a fruit
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04:21 < hprmbridge> kanzure> GRG is not gone
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05:22 < fenn> the www.grg.org subdomain went away and i got confused
05:22 < fenn> grg.org is still there
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06:30 < kanzure> some live tweets from the dublin longevity conference https://twitter.com/statto/status/1692812476725793084
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07:31 < hprmbridge> kanzure> http://biogerontolgy.blogspot.com/2023/08/blogging-at-longevity-summit-2023.html?m=1
07:37 < hprmbridge> kanzure> "3-10% of all babies are born via IVF in developed countries." https://twitter.com/hsu_steve/status/1693936550407508339
07:59 < hprmbridge> alonzoc> Really? Wow that's a surprising stat
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10:25 < hprmbridge> kanzure> https://www.palladiummag.com/2023/08/16/the-only-reason-to-explore-space/
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13:49 < NewtonTrendy> what did you find out?
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15:11 < L29Ah> > Metformin turned out to be a bad move. GLP1 agonists have issues with lean muscle mass.
15:11 < L29Ah> i'm eating metformin for four years, can do the same amount of pullups today as in the beginning and weigh a little more (don't have a good way to measure the muscle mass); can you elaborate on that?
15:18 < CNOT> are you guys druggies? - no i am doing nootropics - pfft
15:20 < hprmbridge> alonzoc> I'm skeptical of the current state of nootropics
15:20 < hprmbridge> kanzure> you don't believe the results are so negative?
15:20 < hprmbridge> alonzoc> I doubt any simple chemical will do anything, the brain is a well balanced machine that's fairly optimised.
15:20 < hprmbridge> alonzoc> No I agree with the negative results
15:20 < hprmbridge> kanzure> what is there to be skeptical about? the data is all pretty lame.
15:21 < hprmbridge> kanzure> no need to invoke balance... we just don't have great nootropics.
15:21 < hprmbridge> alonzoc> True, I just think any nootropic is going to be more complex than "this  small molecule makes brain go brr"
15:23 < hprmbridge> alonzoc> Like yeah the brain might not be performing better because energy trade offs or something, but variations in intelligence due to genetics seems to all be vital genes iirc. I remember the CCR5 mice studies for one were interesting
15:24 < hprmbridge> alonzoc> Yeah skeptical is the wrong term because it's ambiguous. It would be better to have said "I think current nootropics is dog shit"
15:25 < hprmbridge> alonzoc> Like well my morning coffee makes be work better. So yay caffeine I guess?
15:26 < L29Ah> amphetamine > caffeine
15:27 < hprmbridge> alonzoc> I'm yet to take amphetamines and don't plan on taking any time soon. I've likely got ADHD so ehh maybe but /shrug
15:32 < hprmbridge> alonzoc> You get them as bright blue dermadisks?
15:37 < L29Ah> used to obtain it as white/pink powder on the black market, as it's unavailable otherwise
16:05 < hprmbridge> alonzoc> I was making a neuromancer reference
16:16 < hprmbridge> alonzoc> Okay I have an AI question. So complexity priors when written as `e^-H(theta)` have a Hamiltonian which is linear in the entropy of your parameters. So an extra bit of information is an extra unit of "energy" and you wish to minimise energy. Now this makes sense if you don't have resource bounds. However my computer has a RAM limit so you'd think using my total system RAM or beyond should have an
16:16 < hprmbridge> alonzoc> infinite energy cost as it's a hard constraint the probability of a model that saturates or goes beyond my RAM limits should be zero. However you want energy to be differentiable, so you want a energy function that's linear near zero and has singularity at some limit. This sounds like the kinetic energy vs velocity of an object under relativity but is there a way to prove this is the natural
16:16 < hprmbridge> alonzoc> relaxation? Like it's got a bunch of nice properties but I'm not sure
16:19 < hprmbridge> alonzoc> correction: kinetic energy is quadratic in relation to velocity in the low energy limit, but the analogy still holds
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17:51 < hprmbridge> kanzure> can we move or reposition a jetstream in the atmosphere?
17:52 < Hooloovoo> nope
17:52 < hprmbridge> kanzure> think bigger
17:53 < Hooloovoo> it turns out that the atmosphere is big and also complicated
17:54 < L29Ah> with strategic nuclear blasts i think we can
17:54 < hprmbridge> alonzoc> If you've got an insane energy budget and orbital megastructures you could do targeted heating of regions of the atmosphere which would have an effect. But (a) atmospheric dynamics is really chaotic so control is hard and (b) why would you want to? It'd just be easier to terraform venus than do such a scale of geoengineering
17:54 < hprmbridge> kanzure> giant mirrors to redirect sunlight?
17:55 < hprmbridge> kanzure> but can you do that without destroying a city like manhattan?
17:55 < hprmbridge> alonzoc> Orbital megastructures. Yeah at the energy scales involved in global climate destroying a city by rounding errors isn't far fetched
17:57 < hprmbridge> kanzure> jetstream repositioning is a commercial use case for terraforming tech; new york to singapore in under 6 hours would be very commercially interesting.
17:58 < hprmbridge> alonzoc> I think the climate side-effects would be problematic, butterflies and all that. Also, supersonic flight is good enough if you really care about transport
18:01 < L29Ah> i don't think you have problems flying from new york to singapore when you can adjust the jetstreams
18:01 < L29Ah> probably even suborbital flights are dirt cheap, energy-wise, in comparison
18:02 < hprmbridge> alonzoc> And pretty fast
18:03 < hprmbridge> kanzure> And how far away from Manhattan are you parking your space rocket?
18:03 < hprmbridge> kanzure> How many hours in a boat until you get to your rocket?
18:04 < hprmbridge> alonzoc> Well tbh at that scale I'd suggest a lofstrom or orbital ring
18:06 < L29Ah> how many congress sessions until commercial thermonuclear blasts are allowed?
18:06 < NewtonTrendy> we can redirect an asteroid hit so the earth moves further away, what could go wrong
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19:35 < fenn> chatgpt 3.5 gets fine tuning (finally) but with a content moderation filter applied to the training data
19:37 < fenn> meta made a speech <-> speech <-> text <-> text multilingual translation model https://ai.meta.com/blog/seamless-m4t/
19:38 < fenn> cc-nc seems like an amazingly boneheaded choice of license
19:38 < fenn> (only non-serious organizations can use it)
19:40 < fenn> AI people keep throwing around this word "toxic" as if it meant something
19:45 < muurkha> commercial organizations can use works under cc-by-nc licenses\
19:45 < muurkha> they just can't sell copies of them
20:33 < hprmbridge> Eli> https://www.youtube.com/watch?v=oPdkuriBEzo
20:33 < hprmbridge> Eli> caffeine is a nootropic. One of the most effective ones.
21:01 < fenn> muurkha: was that actually clarified somehow or did CC fix the ambiguity in newer versions of the license?
21:02 < fenn> simone collins' secret society was called "Dialog"
21:09 < muurkha> fenn: I don't think there was ever such an ambiguity
21:12 < muurkha> hmm, maybe it's not as clear as I thought it was: https://creativecommons.org/licenses/by-nc/4.0/legalcode
21:14 < docl> to redirect a jetstream, you might try large solar mirror arrays. to do so while only modifying the stratosphere temperature, you could use UVC reflectors. no actual "megastructure" just swarms of flat mirror sats
21:16 < docl> realistic near term orbital rings are less "megastructure" than people imagine them to be also
21:19 < docl> ah, I see kanzure mentioned mirrors already. basically you could add coatings so they scatter anything shorter than UVC. this causes ozone formation and doesn't reach the surface. O3 increases UBV absorption in addition to the direct heat you get
21:20 < docl> lower hanging fruit is probably tropical storm steering, so you can ensure hurricanes don't hit populated areas
21:23 < docl> vyvanse is finally out of patent, but nobody has gotten a generic through fda approval yet so it's still absurdly priced. I'm on dexmethylphenidate ER for now
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21:29 < muurkha> stimulants have real downsides
21:30 < fenn> and real upsides :D
21:30 < fenn> ride the stimulant rollecoaster!
21:30 < fenn> do a loop!
21:30 < muurkha> I mean one Austrian neurologist starts experimenting with cocaine and gets to writing, and we end up with fifty years of pseudoscientific psychoanalysis
21:31 < fenn> is that what happened
21:31 < muurkha> pretty much
21:31 < fenn> arguably cocaine also facilitated the VLSI electronics revolution
21:31 < muurkha> pretty plausible
21:31 < muurkha> harder to tell tho
21:32 < fenn> it was alleged by people who were there
21:32 < fenn> we can do better
21:32 < muurkha> venture capitalists and circuit designers didn't leave nearly as much detailed evidence of their borderline-psychotic thought processes tho
21:33 < fenn> you just have to look at the circuits lol
21:33 < muurkha> you have to have experience designing circuits under the same constraints to read that language, though
21:34 < docl> a reasonable basic orbital ring design looks like: 100-100k tons of metal in a circular orbit. every so often you have a tether, which is held up by modifying the orbit of the ring magnetically at a small angle. the field is mostly induction in the metal (non ferrous, aluminum e.g.). there's some drag which is offset by fast switching coils, but this is relatively low given the high relative velocity. 
21:34 < docl> the orbiting metal is not contiguous, but closely spaced enough to keep the tether top under constant levitation. anyway there's no sheath around the entire length of it (which makes it easier than a lofstrom loop IMO)
21:35 < fenn> launch loop only has a sheath for the first 50km or so, where there's air
21:35 < muurkha> a circuit that is a reasonable if uninspired solution in 01978 might be a stupid blunder, or a brilliant breakthrough, in 01979
21:37 < docl> well by drug abuser standards the ADHD dose is practically microdosing. and you intentionally avoid the sudden hits/lows with lisdexamphetamine or an extended release version. not exactly comparable to snorting coke
21:38 < muurkha> Freud was probably using coke in a very similar way
21:38 < muurkha> most people who chew coca do
21:41 < muurkha> therapeutic doses of stimulants are indeed significantly smaller than the usual recreational doses, though early recreational users often start with therapeutic doses delivered through a faster method of administration (such as, as you mention, insufflation, though that has also been used therapeutically with cocaine, sometimes with disastrous results)
21:43 < fenn> alonzoc: tan(x) is roughly linear near 0 and also asymptotic at +- pi/2, and could be scaled appropriately
21:53 < fenn> log(-1/(x-1)) might do what you want
21:57 < docl> s/shorter than UVC/longer than UVC
22:00 < fenn> ideally you'd scatter only IR (for reducing global warming)
22:11 < docl> visible light would still create a lot of heat lower in the atmosphere / on the ground / in the ocean, messing with the weather that way. UVC only lets you target the stratosphere. given the angle of spread for sunlight (which we're not changing) the spot size diameter is about 1% the distance of the mirror, so e.g. at 10,000km you have a 100km wide spot.
22:12 < docl> (this is for increasing flux, not blocking it)
22:20 < hprmbridge> Eli> @fennfoot do you have an eidatic memory?
22:25 < fenn> not even close, i can barely remember anything before 2 years ago, and i regularly update this memory
22:26 < fenn> i always told myself "i have a fast learning curve and also a fast forgetting curve" but it might just be wishful thinking
22:26 < fenn> piracetam does seem to help quite a lot with recalling details from long ago
22:27 < fenn> other people seem to have an uncanny ability to recall exactly where they learned a fact, but for me it all goes into a general pool of knowledge
22:32 < fenn> wow... elizabeth stromeyer :also could seemingly recall random dot patterns with such fidelity as to combine two patterns from memory into a stereoscopic image"
22:33 < docl> interesting. I seem to be one of the people who remembers where I learned a thing easily. I don't necessarily recall everything I know easily though, often need my memory jogged to summon the fact/claim/info to mind. and I've had experiences where someone else remembers a conversation clearly that I don't recall having
22:38 < fenn> we might all just be giant recurrent hidden markov models, and the dialect or citation style we're raised with (so and so said...) gets ingrained at an early age
22:39 < fenn> if you're raised around people who just state "X" instead of "so and so said X" then maybe you learn to never bother to remember who said a thing
22:40 < fenn> i always had a harder time with names than faces tho
22:40 < fenn> fortunately on irc your name is your face
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