--- Log opened Sun Aug 11 00:00:19 2024
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07:25 < hprmbridge> Eli> New proteomic age clock paper just dropped https://www.nature.com/articles/s41591-024-03164-7
07:28 < hprmbridge> Eli> Seems like the rejuvenation Olympics people are going to have new data points to modulate
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09:56 < hprmbridge> docl> Awesome. I wonder to what extent you can just degrade the unwanted proteins and get a notable effect on reversing aging? How well has senolytics been doing empirically? Probably not enough on its own, as there are other biomolecules (not to mention DNA degradation), and bulkier mechanical influences like scar tissue, plaques, etc.
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16:29 < fenn> is rejuvenation olympics just chronologically old people competing at sports?
16:30 < fenn> aw jeez. 204 proteins associated with aging
16:32 < fenn> that's 1) too many to dig through by hand and examine their interactions and causality 2) too many to target with a drug or biologic and not get crazy side effects due to chance
16:33 < fenn> a lot of them will be responses to dysfunction and are actually helping
16:51 < docl> just because helping doesn't automatically mean not-harming
16:51 < docl> might need to nuke them all simultaneously
16:53 < docl> maybe just see if you can cut them all by 80% in terms of abundance. or something more conservative until you know what direction you're pushing the needle
17:11 < L29Ah> biological aging clocks aren't for eliminating the biomarkers, they are for preliminary comparation of seemingly-irrelevant interventions
17:22 < docl> maybe, maybe not? those proteins aren't just sitting there doing nothing, they're going to have some impact on cell function
17:23 < docl> if not that as the cause of cell dysfunction in aging, then what? cytostructure?
17:27 < docl> dna damage maybe? I read a while back that yeast has two totally different senescence mechanisms and you can switch between them to make they yeast live longer
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17:40 < docl> .t https://www.genengnews.com/news/lifespan-extension-record-set-in-yeast-cells-using-synthetic-gene-oscillator/
17:40 < saxo> Lifespan Extension Record Set In Yeast Cells Using Synthetic Gene Oscillator
17:44 < docl> https://www.science.org/doi/10.1126/science.adh4872 // Genetic circuitry boosts cell longevity
17:47 < docl> apparently if you increase one of the two forms of senescence, the other decreases. so you get 80% longer lifespans by oscillating between the two. hormesis-like...?
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18:15 < docl> .m https://x.com/paulg/status/22319113993
18:15 < AugustaAva> ​twitter: <paulg> Convertible notes have won.  Every investment so far in this YC batch (and there have been a lot) has been done on a convertible note.
18:15 < docl> .t https://corporatefinanceinstitute.com/resources/fixed-income/convertible-note/
18:15 < saxo> Convertible Note - Overview, Main Advantage, Terms
18:18 < docl> (which is mentioned in https://paulgraham.com/hiresfund.html which is mentioned in https://www.ycombinator.com/documents )
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18:30 < docl> "In late 2013, Y Combinator introduced the original safe, or the Simple Agreement for Future Equity. At the time of introduction, startups and investors were primarily using convertible notes for early stage fundraising. The original safe was intended to be a replacement for convertible notes, and it has generally been successful in doing so."
18:30 < docl> FROM https://bookface-static.ycombinator.com/assets/ycdc/Website%20User%20Guide%20Feb%202023%20-%20final-28acf9a3b938e643cc270b7da514194d5c271359be25b631b025605673fa9f95.pdf
18:31 < docl> ugh nastylink pdf
18:35 < docl> fenn: basically this stuff is like the dna of the evolved ecosystem pgraham's ycombinator generated via natural selection, which hacks humans to make investors willing to invest in early stage stuff and founders motivated to make that a good idea
18:36 < docl> if you think of it like single celled organisms undergoing lab evolution it's a bit less intimidating
18:37 < docl> or such is my theorycrafting at this time
19:04 < hprmbridge> kanzure> mech-USPTO-31K chemical reaction data set https://www.nature.com/articles/s41597-024-03709-y
19:05 < docl> has someone yet credibly translated this ycombinator system to a cryptocurrency context? seems like an obvious thing for someone to try
19:09 < docl> or is that what a dao is
19:12 < hprmbridge> kanzure> yes it's called SAFT
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19:26 < docl> is it at all worth considering using a SAFT instead of SAFE in present form? or is it just opening yourself to extra scrutiny and nonsense in practice
19:29 < hprmbridge> Eli> In the paper they have a group of 20 proteins that seem to correlate almost as highly as the 204 protein group
19:30 < hprmbridge> Eli> It’s people basically competing on their hornets clock and posting on a leaderboard I think
19:30 < hprmbridge> Eli> https://www.rejuvenationolympics.com/
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19:41 < hprmbridge> Eli> You can decrease your hba1c by eating less sugar. You can reduce homocysteine by taking vitamin b12. You can modulate this stuff via lifestyle choices. I’m sure people will start comparing their proteomic ages.
19:41 < hprmbridge> Eli>
19:41 < hprmbridge> Eli> The crazy thing is comparing the hazard ratio of diseases between the lowest and highest 5% of proteomic age.
19:57 < docl> ok I'm reading up on the telgram saft fiasco and apparently they left themselves open to an attack by restraining order that forced them not to issue the coins? like the coins couldn't be predetermined to exist algorithmically with a deadman switch kind of thing? this is not how I believed crypto would work at all 10 years ago
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21:12 < fenn> ~2 million chemical reactions 1.4GB compressed https://figshare.com/articles/dataset/Chemical_reactions_from_US_patents_1976-Sep2016_/5104873
21:13 < fenn> not deduplicated
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21:34 < fenn> rejuvenation olympics is kinda useless because we don't know who these people are or what they're doing
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22:05 < fenn> Eli i found this chart compelling https://www.nature.com/articles/s41591-024-03164-7/figures/4 "ProtAgeGap stratifies individuals into divergent age-specific mortality and disease risk trajectories"
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23:02 < hprmbridge> Eli> Yep, the hazard ratios are crazy. So, the hypothesis would be then, "if I modulate these proteins by chaning lifestyle/supplements, can I have a better healthspan?"
23:41 < fenn> ohh the hazard ratio is 1.16 *per year*
23:43 < fenn> 1.1 all cause mortality
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--- Log closed Mon Aug 12 00:00:20 2024