--- Log opened Wed Mar 12 00:00:43 2025
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06:52 < hprmbridge> Eli> Yeah I didnt understand the 3d genome change part. I think the part about cells having a maximum of 3000 mutations was interesting. I’d like to see this stuff replicated to know if it’s legit. And I’d like to see more animals on the graph. But if there’s predictive accuracy, then I’m wondering if it may act as another predictive “aging clock” like the horvath clock or biological age blood testing.
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10:20 < NewtonTrendy> https://longevity.pink/featured-studies/
10:26 < RangerMauve> Neat https://pubmed.ncbi.nlm.nih.gov/36638792/
11:15 < ike8> > Neat https://pubmed.ncbi.nlm.nih.gov/36638792/
11:15 < ike8> ya boi David Sinclair
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15:49 < hprmbridge> Eli> I’m not gonna say Sinclair is wrong, but there probably needs to be replication with everything this guy does.
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17:42 < fenn> getting just one high quality genome of the individual would be a step up from the current state of care; asking for dozens of genomes in order to estimate mutation load is currently expensive
17:43 < fenn> maybe you can get lucky and there are certain tissue types that mutate at a strongly correlated rate wrt aging
17:44 < fenn> i still think almost all aging clocks are completely useless for actually doing anything, since we have no theory
17:44 < fenn> it's circular reasoning
17:44 < L29Ah> fenn: they are a starting point for experimenting
17:45 < fenn> as soon as it becomes an "aging clock" it's a metric to be gamed
17:45 < L29Ah> given we can't directly measure interventions' impacts on human lifespan
17:45 < L29Ah> sure, but we don't have anything better yet
17:46 < fenn> there needs to be some constraint like, the intervention has nothing to do with the measurement (the aging clock)
17:47 < fenn> otherwise you're just lying to yourself
17:47 < L29Ah> perhaps after attaining several-fold lifespan gains (not necessarily through systemic interventions) we could estimate various rates of decay of organs and replace them as needed
17:48 < L29Ah> fenn: might be adjusting the clock markers by itself could make the organism more resilient, but yes
17:48 < fenn> yes there will probably be a lot of weird new problems that crop up once the root cause of the main ones are dealt with
17:49 < fenn> if you use epigenetic markers as your aging clock and then intervene with OSKM to change epigenetic markers, maybe it will have positive effects on the rest of the systems, but by measuring only epigenetic markers you really have no idea. directly modifying the metric is circular
17:54 < L29Ah> you are beating up a strawman
17:54 < fenn> i hope so
18:13 < fenn> sinclair's ICE mice look old
18:14 < fenn> so much so that i was confused about the figure labels
18:15 < fenn> possibly confused about the entire study, didn't get good sleep
18:16 < fenn> ok so they are supposed to look old. "faithful DNA repair advances aging" and this is what they're inducing
18:42 < fenn> @eli if you don't already know about it, ask your favorite AI for an explanation of how DNA methylation causes histone deacetylation and chromatin compaction. i wish i had a nice 3d animation to point to
18:43 < fenn> the 3d structure of the DNA is how methylation silences or activates gene expression. some genes are activated by methylation but most are silenced
18:46 < fenn> also simply being in the open un-compacted state will increase the rate at which DNA is methylated
19:06 < fenn> https://link.springer.com/book/10.1007/978-3-030-68670-3 free book
19:07 < fenn> .t
19:07 < saxo> Introduction to Epigenetics | SpringerLink
19:09 < fenn> i couldn't find a simple taxonomy of the different classes of genes that get turned on or off with methylation. some possible keywords: bivalent domains, poised, stably repressed, plastic genes, stable genes
19:10 < fenn> alpha-ketoglutarate keeps popping up (TET demethylase cofactor)
19:27 < fenn> somewhat unrelated: "DNA extracted from the [dead sea] scrolls can be used to sort different scroll fragments not only based on the animal species but also based on variations in the nuclear genome of individual fragments."
19:28 < fenn> oh that's probably just "this specific individual animal was turned into this one scroll" not "this region of skin cells is more similar due to somatic mutations during development"
19:35 < hprmbridge> kanzure> https://ai.pydantic.dev/graph/
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19:55 < fenn> not a bad animation:
19:55 < fenn> .t https://youtu.be/Tj_6DcUTRnM
19:55 < saxo> Epigenetics Overview
19:55 < fenn> doesn't show the large scale changes in DNA structure though
19:59 < fenn> this has more large scale conformation changes but it's kinda cartoony and inaccurate and doesn't give any specifics:
19:59 < fenn> .t https://youtu.be/XelGO582s4U
19:59 < saxo> Chromatin Biology: Epigenetics and the Regulation of Gene Activity
20:02 < fenn> the chromosome animation in particular is off by a few orders of magnitude
20:13 < fenn> .t https://youtu.be/Pl44JjA--2k?t=1m
20:13 < saxo> Die 3D-Organisation unseres Genoms
20:14 < fenn> except not german
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20:44 < docl> I wonder why there aren't more single celled organisms that descend from cancers of complex multicellular organisms? hela and transmissible dog cancer are examples, but those are from recent evolutionary history, you'd think the animal kingdom would produce novel eukaryotic microbes every so often
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21:13 < docl> there's a few more examples here https://en.wikipedia.org/wiki/Clonally_transmissible_cancer
21:32 < docl> there's a species of soft-shell clams with a cancer that can infect through seawater 100 miles away. so it's perhaps a candidate for something that could break away and become a novel animalia-descended protist. seems strange not to have examples of that happening already... perhaps the cell mechanisms in animalia are just really shoddy for the microbial niche (prioritizing error correction over 
21:32 < docl> replication speed) so they can't ever find a niche where they are competitive?
21:34 < docl> oh, here we go https://biologydirect.biomedcentral.com/articles/10.1186/s13062-019-0233-1
--- Log closed Thu Mar 13 00:00:44 2025