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Agree with all the above comments. Making a bunch of rapid DNA cuts outside of genes is not all that convincing of a model for aging. "The mice began to look an
by subroutine 4y ago
Agree with all the above comments. Making a bunch of rapid DNA cuts outside of genes is not all that convincing of a model for aging. "The mice began to look and act old". You could say that about someone exposed to massive amounts of nuclear radiation - they move slow, they hurt all over, their skin sluffs, etc. Also afaik, aging has been linked to telomere depletion after many cell divisions - not the cumulative effects of random DNA cuts. Lastly, I have reservations about the author's statement that this approach is better "because it’s easier to manipulate epigenetic molecules than to reverse DNA mutations". This might be true if they are globally altering DNA methylation or acetylation. But that will surely have its own side-effects due to globally altering gene regulation. However if it turns out that it'd be best to only target particular methylomic sites, it will be similarly difficult to implement. In general, it's typically better to be precise when it comes messing with DNA and gene expression - of course the tradeoff is that being precise is very difficult. I'm interested to read the original article, to see what they've actually done. as it is my sentiment is the same as those above - I'll get excited when their method significantly extends the lives of mice that have underwent otherwise normal aging.
- generalizations 4y ago> You could say that about someone exposed to massive amounts of nuclear radiation - they move slow, they hurt all over, their skin sluffs, etc. Sure. But that's only half of it. What's promising is when, afterwards, you give that person a gene therapy which reverses the aging-adjacent damage.
- subroutine 4y agoMy point here is they might have given a gene therapy that reverses radioactivity exposure damage, not age-adjacent damage. More specifically their model for harming cellular DNA seems to have been chosen because harming DNA in this specific way can be fixed by their proposed therapy reagent. They did not choose this model for because it most closely matches aging processes irl. Their model passes only because the mice 'looked old'. Lots of things can make an animal have elderly phenotypes (radiation exposure for example). And you might find something that reverses those phenotypes without actually finding anything that would mitigate natural aging (because their etiologies are completely different). It would be like giving an antibiotic to treat a viral infection.
- generalizations 4y agoA while back I fell down the anti-aging rabbit hole, and it was fascinating to realize that we have no good way to measure aging. We can measure different things that seem associated with it, but I guess since we don't know the root cause(s), we don't have any one thing we can all agree on. It seems like the only thing everyone can agree on is that if a person looks old, they (probably) are. Which is a long way of saying, yes, I agree with you; the methylation metric may be total bunk. But there isn't anything else (IIRC) that we can all agree to measure instead. That's why the Harvard article emphasized that they were using a metric for aging they'd developed in-house. I just want to read the paper before passing judgement, and right now sci hub doesn't have it.
- subroutine 4y agoDue to a past experiment in my lab by a post doc, I'll be forever skeptical of putative treatments for complex human diseases that were identified using rodent models that target a narrowly defined set of behaviors or phenotypes. The experiment was to test whether vitamin D supplements could attenuate behavioral problems associated with fetal alcohol syndrome. Our lab used a rat model of FAS. When the post doc told me about her experiment idea, I (as an undergrad at the time) told her it was interesting but couldn't be performed in a rat model because vitamin D was poison to rats. It calcifies their skin because they cant break D down like humans can. My warning was ignored, and the experiment was conducted anyway. She found that vitamin D treatment mitigated hyperactivity associated with FAS, and presented this finding at conferences. Well no shit this treatment would reduce activity in rats. If my skin was calcified I wouldn't want to move either.
- 93po 4y agoThe exact ratio of blame assigned to reasons for increased risk of death over time are still not really settled or universally agreed upon.