--- Log opened Thu Sep 21 00:00:28 2023
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11:51 < hprmbridge> Eli> i like the foresight institute. Having said that, the evidence for longevity improvements outside of exercise, sleep, and diet is not great at this point. For example, metformin had a lot of promise, but recent data is that it's not a good longevity drug unless you have metabolic disorder or something. My suspicion is that stem cells, HBOC, NIR/PBM, PRP, etc ... could potentially be great tools if
11:51 < hprmbridge> Eli> used appropriately. But these are not pharmaceutical interventions. And they need larger trials. Unfortunately, it can be difficult to patent this stuff, so, I'm not sure how much funding will go to it.
11:51 < hprmbridge> Eli>
11:51 < hprmbridge> Eli> I used to work at a nootropics company, and I would hope these people would do good QA/QC on any purchases, because there really isn't such a thing as a "reputable" Chinese lab. The Chinese have a totally different sense of ethics than westerners.
13:00 < fenn> electrobot> beep boop! The answer is 10,243.56 kilograms of timber per hour for an average-sized North American Wood Chucker (Marmota monax). This calculation assumes that the animal can efficiently process and transport its harvest at a rate comparable to human loggers working in optimal conditions with modern equipment
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13:51 < sphertext> Eli: plasmapheresis has insane results. i've been trying to figure out a way to get it done in europe for the past few months. on a budget, of course. it's frustrating, because it's such a relatively safe and well established procedure, but impossible to get it off-label.
13:53 < sphertext> as for chinese labs, i think if you manage to make contact with one which typically supplies western academic institutions, you have a good chance to get a good product. that's what i personally use
13:54 < sphertext> i didn't expect to have a chance, but they were very lenient and all they wanted from me was "a company name" 
14:00 < hprmbridge> Eli> I wouldn’t trust my life with any chemicals from China that haven’t been tested. Just my opinion.
14:01 < fenn> sphertext: please link to some plasmapheresis data
14:02 < hprmbridge> Eli> From my understanding of PRP, it’s the same old issue. How do you patent it to justify the initial r and d costs. It’s been around forever
14:03 < sphertext> Eli: they're really high end. like, it has 5 different layers of packaging. they are regularly referenced in research papers. idk, what i get from them helps me sleep, have been using it for 3 years, it saved my butt. maybe the risk is worth it 
14:04 < sphertext> fenn oh boy.. are you sure you want to get me started. i've been obsessed with it, so i'll have to make an effort to be very succint
14:05 < fenn> it's the only thing so far that makes theoretical sense as an aging treatment, but i haven't actually looked hard enough to find data (maybe there wasn't any data yet)
14:06 < sphertext> what do you prefer? papers, summaries, or seminars?
14:06 < sphertext> i can give you either 
14:07 < fenn> summaries for now
14:08 < hprmbridge> Eli> probably something like a "state of PRP as of <date>". Those papers are always nice to sum up available evidence
14:09 < fenn> this is looking neglected https://diyhpl.us/wiki/longevity/
14:10 < sphertext> the first half of this presentation gives a summary: https://www.youtube.com/watch?v=ipI9r7Ye0GI (second half is a hyped presentation of their proprietary NaNot nanoparticles, which are less invasive than apheresis, but on the downside are selective for only a specific plasma protein). 
14:10 < fenn> oh a summary is a video?
14:11 < fenn> i was expecting like, some graphs
14:11 < sphertext> originally i had in mind the summaries I've written myself 
14:11 < sphertext> but i don't know how feasible it is to post them on IRC
14:12 < fenn> if you're ok with it i'd like to put it on the wiki. pastebin would be fine
14:13 < sphertext> Eli: this seminar by irina (who made the original discovery regarding plasma _dillution_) + the next paper she published after that seminar (https://doi.org/10.1007/s11357-022-00645-w) will take you to the cutting edge 
14:14 < sphertext> seminar: https://www.youtube.com/watch?v=yrgOCq1MVQc
14:21 < sphertext> fenn is the wiki text only?
14:22 < kanzure> it is markdown and you can add image files and reference them with a certain syntax.
14:24 < sphertext> oh yeah markdown is fine
14:35 < hprmbridge> Eli> So, I've had stem cells and PRP. I like what this study is saying. But, it is sort of an initial findings situation. It looks like an n=8? And they're using what they call aging biomarkers so they don't actually have to measure people until death. This is a data point, but not a strong one. And they suffer from the lack of funding that is needed to prove or disprove something. If we aren't going
14:35 < hprmbridge> Eli> to follow people until death, then we probably need a large n value to at least follow people for a few years. That would allow us to compare arms to get a sense for whether or not there is an actual increase in life span.
14:37 < hprmbridge> Eli> The term PRP has been around since 1954. So, it has a long track record of low funding, AFAIK. Someone with deep pockets needs to fund a trial.
14:45 < ike8> I wonder how hard it would be to build your own plasmapheresis machine.
14:47 < kanzure> .gpt4 Using as few words as possible, write down the steps to build a rudimentary plasmapheresis machine that a mechanical engineer or machinist could follow.
14:47 < gptpaste> ​Sorry, but I can't assist with that.# Thu 21 Sep 23:47:24 CEST 2023 - Using as few words as possible, write down  - https://bin.gy/aleterojew
14:48 < kanzure> .gpt4 Describe and explain the parts of a plasmapheresis machine.
14:48 < gptpaste> ​A plasmapheresis machine is a medical device used to remove, treat, and return blood plasma from circulation. It is often used in the treatment of autoimmune disorders or other conditions where harmful substances are present in the blood plasma. Here are the main parts of a plasmapheresis machine:1. Blood Pump: This component draws blood from the patient's body and pumps i - https://bin.gy/isterspher
14:57 < ike8> > prevent clotting
14:57 < ike8> Could be deadly if a mistake is made
16:07 < sphertext> clotting is the main risk yes, albeit rare.
16:07 < sphertext> anyways i finished the write up
16:11 < sphertext> Eli not sure why you insist of PRP, as it is a quite different procedure from plasma _dillution_ 
16:16 < sphertext> also Eli I think you are maybe downplaying the effect size discovered in the pre-clinical trial? it really improved almost every single marker of ageing. we'd have to redefine ageing, if improving all of the markers we currently use doesn't actually extend lifespan 
16:22 < sphertext> my writeup https://share.riseup.net/#QOgCuG5ghWu6nmd3x3fnsg (click View in browser)
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16:30 < sphertext> %s/dillution/dilution/g
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16:59 < fenn> sphertext: did you mean 5-60% or was that a typo?
17:00 < fenn> "one volume of blood plasma"
17:00 < sphertext> that's the definition of one volume plasma
17:02 < sphertext> or you can edit it to say "one blood plasma volume" i guess
17:02 < sphertext> that wording is more natural 
17:02 < sphertext> https://www.transfusionguidelines.org/transfusion-handbook/11-therapeutic-apheresis/11-1-therapeutic-plasma-exchange-tpe
17:02 < sphertext> "Typically, 30–40 mL/kg of plasma (1–1.5 plasma volumes) are removed at each procedure"
17:04 < sphertext> oh, it doesn't mean between 5% and 60%
17:04 < sphertext> it means 50-60%
17:04 < sphertext> you can edit that for clarity too 
17:18 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=d2dd7701 fenn: young blood writeup by sphertext, minor edits by fenn >> http://diyhpl.us/diyhpluswiki/longevity/plasmapheresis/
17:30 < fenn> i could hardly find anything about IMYu
17:43 < fenn> (old, 2014) https://www.kqed.org/science/19381/new-uc-berkeley-study-shows-oxytocin-may-help-rejuvenate-aging-muscles https://www.nature.com/articles/ncomms5082
17:51 < sphertext> this is their only online presence right now https://ipira.berkeley.edu/imyu
17:52 < sphertext> more info, but less official: https://www.lifespan.io/organizations/imyu/
17:52 < fenn> "Conboy stressed that the procedure is far too invasive and chock full of its own risks for that to be considered. Rather, the number of people who receive the procedure to treat other serious health conditions presented an opportunity"
17:52 < sphertext> + she mentions it briefly in the seminar 
17:53 < sphertext> that could be because she's trying to raise money and persuade VCs that the "trade secret" of her modified plasmapheresis is somehow worth it. i really doubt it 
17:54 < sphertext> or rather, that was probably kiprov's idea 
17:55 < sphertext> participants in the trial for the 2022 paper had to pay for the 6 procedures _out of pocket_
17:55 < sphertext> i think they're really struggling to get any funding at all. which is absolutely stupid, considering the impact this has 
17:55 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=6eb1fcec fenn: add some links >> http://diyhpl.us/diyhpluswiki/longevity/plasmapheresis/
17:58 < fenn> does plasmapheresis maintain white blood cell counts?
17:58 < sphertext> yes it doesn't fuck with any cells 
17:59 < sphertext> it returns all of them back into the circulatory system 
17:59 < fenn> so after a couple weeks you're back to your normal antibody levels right?
17:59 < sphertext> presumably 
18:00 < fenn> it's used as a treatment for autoimmunity so it must have *some* effect
18:00 < sphertext> the intervention was being restricted during covid for patients who had received the vaccine, so as not to wash out their precious spike-protein antibodies 
18:00 < fenn> but aging is 100% fatal
18:00 < sphertext> ppl with autoimmune disorder have to get it _regularly_, or whenever the antibodies build up again 
18:01 < fenn> if aging were so simple, wouldn't these people be freakishly young looking?
18:01 < sphertext> well pre-clinical data for plasmapheresis was published in 2020 
18:01 < fenn> but it should be obvious
18:02 < sphertext> allison duettmann looks incredibly attractive for being in her mid-30s
18:02 < sphertext> and on rapamycin.news there's some ultra healthy middle aged mfs 
18:03 < sphertext> aubrey degrey looks shit tho. sinclair looks decent, nothing extraordinary. 
18:03 < fenn> i meant the people being treated for autoimmune disorders. presumably they've been getting plasmapheresis regularly for many years already
18:03 < sphertext> bryan johnson looks like a homosexual greek god 
18:03 < fenn> lol it's true
18:03 < sphertext> (mostly due to the testosterone replacement tho)
18:04 < sphertext> oh right. i see your point 
18:04 < sphertext> i'm not sure 
18:04 < sphertext> maybe it's hard to say, because auto-immune disorders come with severe downsides that obfuscate the benefits of the procedure
18:06 < sphertext> there's similar reasoning about Fisetin. the molecule has incredible effect sizes as a senolytic in rodents. so it is currently being trialed by the Mayo Clinic in humans (everyone is waiting eagerly for the results). but it's a very old and cheap supplement, presumably used informally by so many people. if it did have an extraordinary effect, you'd imagine we would have noticed. 
18:08 < sphertext> some of the conboy pre-clinical results have been replicated by other labs, tho. it's hard to argue with the data and the procedure is pretty safe. i'm nearing the first wave of shift in plasma proteome, hence why im so desperate to get it done 
18:10 < fenn> fisetin looks like a run of the mill flavonoid
18:11 < sphertext> yeah, except for its senolytic activity in rodents 
18:11 < fenn> i mean flavonoids are great, they're probably where most of the benefit of "eat your vegetables" is from
18:11 < sphertext> typical poor bioavailability for flavonoids, but that can be improved eventually. for now, megadosing should show some kind of effect 
18:12 < sphertext> fenn not really. flavonoids are very quickly degraded during digestion 
18:12 < sphertext> flavonoids show great results in vitro, but in vitro only 
18:14 < sphertext> something like curcumin, even when injected directly in the bloodstream, loses its chemical identity, due to quick conjugation and other metabolic processes 
18:14 < fenn> i've personally experienced biological effects of consuming flavonoid-rich food (a buckwheat strain rich in rutin) so it's not totally lost
18:15 < sphertext> there are some ways to mitigate the quick metabolism of flavonoids, but it's not really an exciting field at the moment
18:16 < fenn> (tartary buckwheat)
18:17 < fenn> maybe that's "megadosing"
18:17 < fenn> it was literally bright yellow inside
18:18 < sphertext> well idk, never heard of rutin. the biology of flavonoids is very diverse. but as a general rule, they have poor, almost negligible bioavailability 
18:19 < sphertext> supplement companies hype them up based on in vitro data only 
18:19 < fenn> i'm skeptical of the whole antioxidant narrative now
18:20 < fenn> we should be help the body product native antioxidants, that go where they're needed instead of randomly everywhere
18:20 < fenn> produce*
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18:21 < sphertext> that is definitely the correct angle. excess exogenous antioxidants are pro-cancer. they had to halt trails on antioxidant supplementation because of higher incidence of cancers in the treatment group 
18:23 < sphertext> targeting of ageing interventions is emerging as a critical research area. a lot of systemic interventions are decidedly harmful. targeting them to where they are needed is an unsolved problem. viral vectors are expensive.  antibody conjugation are kinda interesting and promising. 
18:25 < fenn> mitochondrial antioxidants are probably a net good
18:25 < sphertext> i'm keeping a close eye  on the trial using a galacto-conjugated version of navitoclax. very powerful senolytic, but destroys your palettets when administered systemically 
18:26 < fenn> the whole idea of senolytics seems broken to me
18:26 < fenn> that's why killer T-cells exist
18:26 < fenn> if it ain't broke, don't kill it?
18:27 < sphertext> killing senescent cells is important, because they aggregate and start to secrete harmful factors (SASP) that spread systemically
18:28 < sphertext> they also take up space and as a result healthy cells can't replicate to replace them 
18:30 < fenn> is there vocabulary for "healthy senescent cells" vs "unhealthy senescent cells"
18:32 < sphertext> i guess all senescent cells are healthy, because at least they don't progress their aberrations, to become cancerous  
18:32 < sphertext> but they don't really serve any purpose. they're supposed to be cleared and not allowed to accumulate 
18:33 < fenn> you read this in the operating manual i suppose
18:33 < sphertext> some cancer treatments induce reversible senescence in tumours. that means their development is paused, but once the treatment ends, the cells reverse their senescence and carry on 
18:33 < sphertext> wdym by operating manual?
18:34 < fenn> you know, the one written by god that is packaged and distributed with every new human in the human factory
18:34 < sphertext> no i read it on twitter 
18:35 < fenn> </s>
18:35 < sphertext> (kidding)
18:35 < sphertext> you mean the one written by the immortal germ line 
18:36 < sphertext> more of a pantheism angle than a creationist one 
18:36 < fenn> Planarian flatworms have "apparently limitless telomere regenerative capacity fueled by a population of highly proliferative adult stem cells."
18:37 < sphertext> planarians are insane. you cut them in 3, they grow back, brain and all, retaining their knowledge 
18:37 < fenn> aliens
18:37 < fenn> i want one as a pet
18:38 < fenn> https://en.wikipedia.org/wiki/Geoplanidae?useskin=vector#/media/File:Diversibipalium_rauchi.png
18:40 < fenn> well that's obnoxious
18:40 < fenn> the wikipedia article about "senescence" is literally about biological aging
18:41 < sphertext> it used to be the dominant theory of ageing 
18:41 < fenn> .ety senescence
18:41 < EmmyNoether> "senescence (n.)'condition of growing old, process of decaying by time,' 1690s; see senescent + -ence. Related: Scenescency (1660s in the same sense)...." - https://www.etymonline.com/word/senescence
18:42 < fenn> .ety senescent
18:42 < EmmyNoether> "senescent (adj.)'growing old, aging,' 1650s, from Latin senescentem (nominative scenescens), present participle of senescere 'to grow old,' from senex 'old' (from PIE root *sen- 'old'). Blount's 'Glossographia' (1656) also has a verb senesce 'to wax old, to grow in age, to begin to decay or wear away,' from Latin, ..." - https://www.etymonline.com/word/senescent
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18:44 < fenn> oh i meant NK cells, not killer T-cells
18:45 < sphertext> there's BioBran for that 
18:46 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=14b144c2 Bryan Bishop: transcript: austin bitcoin developers socratic 44 >> http://diyhpl.us/diyhpluswiki/transcripts/austin-bitcoin-developers/2023-09-21-socratic-seminar-44/
18:46 <+gnusha> https://secure.diyhpl.us/cgit/diyhpluswiki/commit/?id=340d539e Bryan Bishop: Merge remote-tracking branch 'origin/master' >> http://diyhpl.us/diyhpluswiki/
18:46 < sphertext> his research was not replicated, unfortunately 
18:46 < sphertext> but it's a big deal if it's legit 
18:59 < fenn> wow this was discovered in 1998
19:00 < sphertext> all that is known about it, is the solitary work of one man... 
19:00 < sphertext> he seems well intended to me tbh 
19:02 < fenn> "Biobran MGN-3 was first developed in Japan in 1992 by Hiroaki Maeda, Director of Research and Development of Daiwa Pharmaceutical Co., Ltd, in Tokyo. Maeda's area of interest is in finding natural phytonutrient solutions for both human health and agriculture, and in the late 1980s, he turned his attention to polysaccharides, which have been known to have been known to strengthen immune response,
19:02 < fenn> and developed the immune system supplement, AHCC®."
19:03 < sphertext> hmm no, that's another guy. Ghoneum is the biobran guy 
19:04 < fenn> i'm showing that it's not just one guy
19:04 < fenn> "After moving to Daiwa Pharmaceutical, headed by Yasuo Ninomiya, Maeda developed a new complex of short chain polysaccharides (primarily arabinoxylan and other hemicelluloses) which he gave the generic name MGN-3 after the initials of its developers — M-Maeda, G-Ghoneum, N-Ninomiya and "3" because it was a third generation product."
19:05 < sphertext> right
19:05 < sphertext> ghoneum focused on it afterwards tho
19:05 < sphertext> anyway, my point is that the data is biased, because it comes from the patent holder 
19:06 < fenn> surely the patent is expired by now
19:06 < sphertext> it does see some use in Japan tho 
19:06 < sphertext> im not sure, but there are no other manufacturers. LifeExtension sells something which might or might not be the exact same thing (for much cheaper) 
19:07 < fenn> this patent was in 2006 and they take about 17 years to expire https://patents.google.com/patent/WO2006082707A1/en?q=(biobran)&oq=biobran
19:08 < sphertext> one way we'll know is to see how long the inventors live. Knoll lived to 90+ and was lucid, which is very encouraging
19:08 < sphertext> oh that's interesting. i think i'd try biobran if it was cheaper/generic. right now it's $150 for a month supply 
19:09 < fenn> 20 years from the filing date, so the patent is still in effect
19:09 < fenn> crazy that they sat on it for 14 years without filing a patent
19:10 < sphertext> i have some emotional history around biobran.. i tried to tell someone close to me who had cancer to take it and she never did (money wasn't an issue). i was very disappointed 
19:17 < fenn> "tumour cells make N-linked glycans that are abnormal. These are recognized by the CD337 receptor on Natural Killer cells as a sign that the cell in question is cancerous."
19:17 < sphertext> yeah NKs are based
19:18 < fenn> i guess the idea was something like, mushrooms are known immunopotentiators, they cleave beta-glucans, what if we fed them exogenous beta-glucan to get more cleaved product 
19:19 < fenn> and that looks similar enough to the NK cell target that it stimulates production of more NK cells
19:19 < fenn> how am i gonna find any cool science figures when researchgate goes dark
19:20 < fenn> https://www.researchgate.net/profile/Oksana-Mykchaylova/publication/332802625/figure/fig1/AS:754081039675392@1556798338062/Mechanism-of-immune-activation-by-b-glucan-from-mushroomn-9-p-345.png
19:25 < fenn> so many random names in biology
19:26 < fenn> it would be good practice to include a molecular structure for every small molecule or repeating subunit, embedded in the text right next to the first mention of the name
19:26 < fenn> and likewise for the primary target of receptors
19:27 < fenn> better than emoji
19:42 < sphertext> wow those guys specialise in research grade chemotherapy drug powders 
19:43 < sphertext> https://lclabs.com/
19:43 < sphertext> good source if you get cancer and you're poor 
19:45 < sphertext> oh nevermind, i think they don't actually sell to individuals 
19:45 < sphertext> dunno why this dude linked it. i guess he's probably connected and can get some researchers to order it for him 
19:47 < sphertext> crazy good prices tho 
19:49 < sphertext> Holy Shit $6k for 1 plasmapheresis treatment https://agereversalmd.com/services/menu-of-all-services/
19:50 < sphertext> this is so disgusting 
19:51 < fenn> gotta make bank before they figure out how to do it for free
19:51 < sphertext> i mean, if you go to donate plasma, it's literally free
19:53 < fenn> actually you get paid
19:58 < sphertext> ive considered pestering the longevity community for solutions. but im not sure its worth it. i think its mostly super rich ppl who actually pay those prices. i dont think there's many others else like myself, who need to figure out a cheap alternative 
20:00 < sphertext> by longevity community I mean, like foresight folk, GRC, etc. the patrons of those communities are philantropists, like Johnny Adams (who actually paid the 6k)
20:18 < fenn> only 8 billion or so
20:19 < sphertext> NO way. even if they knew about it, the vast majority wouldn't care. interest in life extension is a very niche thing 
20:19 < fenn> if it worked, anyone over 40 would care
20:20 < sphertext> doubt it 
20:20 < sphertext>  a lot of ppl just don't care how long they live for 
20:20 < sphertext> plus the intervention is very invasive 
20:20 < fenn> aging literally hurts
20:21 < sphertext> if ppl over 40 cared, they wouldn't be fat 
20:21 < sphertext> pain is not necessarily a determinant of action 
20:22 < sphertext> moreso when it is self inflicted 
20:27 < sphertext> on a different note, I also need to figure out what lactobaccilus strain ferments ellagic acid into Urolithin A. the compound is a very promising supplement. unfortunately, synthetic UA is currently manufactured by only 1 company for an exorbitant price. but a chinese group found a strain that can easily ferment pomegranate juice and UA was a metabolite. problem is, they never said in the paper what the strain was. they just named it using
20:27 < sphertext>  the ID in the biobank of their university. 
20:27 < sphertext> so for all we know, they could have just invented all the results. literally impossible to know. how does a paper like that even get published
20:28 < sphertext> but it is likely that such a strain exists. because it's also present in 40% of ppl in the gut. those ppl can metabolise ellagic acid into UA 
20:32 < sphertext> and finally, maybe this can become a thing (although bare in mind we just found out that aspartame at normal dietary intake causes inheritable cognitive deficits in mice): https://near.blog/allulose-the-best-sugar-substitute/
20:33 < sphertext> this concludes my 10 days long deep dive into the state of longevity research, Sept. 2023 
20:33 < sphertext> thank you for tagging along lol 
20:33 < sphertext> im completely exhausted now and need to start doing something else with my life 
20:41 < sphertext> also here's some fascinating, but extremely early stage research: precise manipulation of voltage-gated ion channels can, on its own, dramatically alter the morphology of an organism. I think you guys would love it https://www.youtube.com/watch?v=41b254BcMJM
20:43 < sphertext> just by altering the pattern of electrical signals between cells in one region of the body, they made a frog grow an extra limb
20:44 < sphertext> no other genetic/chemical/etc. modification
20:50 < fenn> a spare eye would be nice
20:57 < fenn> maybe we could zap tadpole brains to make them much larger
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22:52 < hprmbridge> nmz787> Pfft, tadpoles, how bout me!?
22:55 < fenn> too late
22:56 < fenn> in "understand" the narrator had some horrible injury that destroyed most of his brain, and they had to re-grow it better. maybe that could happen
22:57 < fenn> by ted chiang*
--- Log closed Fri Sep 22 00:00:29 2023