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Loss of epigenetic information can drive aging in mice
- sinenomine 4y agoIt would be more interesting if this paper studied low-level molecular pathology of ageing, i.e. protein crosslinks, advanced glycation end-products, etc. These pathologies are going to remain even after the supposed fix of epigenetic decay.
- robwwilliams 4y agoYes, and mitochondrial DNA integrity; and telomere length; and metabolic rate; and cancer surveillance efficiency; and stem cell exhaustion; and immune balance; and, and so on. Let’s face it—-aging is wonderfully complex.
- vrc 4y ago“Study in mice implicates changes to way DNA is organized, regulated rather than changes to genetic code itself” What??
- thaumasiotes 4y agoThe genetic code is the same in every cell, a complete specification of the organism. But cells are highly specialized. For example, you only grow nails on the tips of your fingers and toes. This is due to what your pulled quote characterizes as organizational effects. The level of activity [protein production] of a given stretch of DNA varies wildly from cell to cell. Structural features are attached to the DNA that make it more or less likely to be expressed. What it would produce if it were expressed ("the code itself") doesn't change. For this analogy, you can think of your genome like BusyBox: a single unified executable that will do wildly different things depending on how you call it.
- gausswho 4y agoIs it not wasteful for each of our cells to contain genetic code for the whole of the organism? Any particular cell only expresses a tiny subset of that code. Are there any organisms that don't follow this approach? On the other hand, there is a satisfying romance to it all. That a cell is borne and joins into the system ready to grow into anything. It makes our 'self' feel like a co-operative experiment.
- thaumasiotes 4y ago> That a cell is borne and joins into the system ready to grow into anything. That generally doesn't happen; a single-cell fertilized egg will grow into the whole organism, but the more usual birth of cells, from the division of an older already-specialized cell, preserves the older cell's existing epigenetic markings. > Is it not wasteful for each of our cells to contain genetic code for the whole of the organism? Depends on your point of view. From an evolutionary perspective, DNA is the part of you that replicates and so having more copies of it is its own reward.
- Rury 4y agoThis is likely an open question. I'm not an expert, but I'd imagine the main reason (at least our) cells all contain genetic code for the whole organism, is largely because stem cells contain genetic code for the whole organism. If stem cells didn't have genetic code for say, both heart cells and lung cells, then it couldn't turn into those types of cells. And since all cells, stem from stem cells... then they also end up with the genetic code for the whole organism. Additionally, DNA is regularly used for creating proteins a cell needs for various purposes. Having extra genetic material than necessary, probably provides some benefits in terms of robustness. Like imaginably when a cell is exposed to a toxic substance, and has genetic code (recipe) for a protein that can neutralize it. Maybe 99% of the time it never needs that genetic code, nor is unnecessary to the cells particular function, but having it around can be beneficial in those rare circumstances. So is it wasteful and bad? Perhaps, but it likely also comes with some positive tradeoffs.
- dekhn 4y agoDNA is "organized" into three dimensional structures which are only partly dependent on the genetic sequence in the region. It's like a rope that's tied up in knots, or twists. Regulation of that structure has huge implications on the accessibility of regions of code, such that regions that are locked inside can't be transcribed into DNA. The management of this complex 3d structure has huge impacts on phenotype, without modifying the code.
- qup 4y ago> “We hope these results are seen as a turning point in our ability to control aging,” said Sinclair. “This is the first study showing that we can have precise control of the biological age of a complex animal; that we can drive it forwards and backwards at will.” Wow.
- slibhb 4y agoLet's see some 20 year old mice before we get our hopes up.
- qup 4y agoI'll settle for 2.5 year old mice that look like 10 month olds. But no, I'm getting my hopes up. And I didn't start today.
- mouse_ 4y agoCheers to getting our hopes up. Hope is pretty cool.
- hdespiritu 4y agoHopium is a powerful drug
- subroutine 4y agoAgree 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.
- polishdude20 4y agoSo the next thing to do is see how long you can keep mice alive then right? If this can reverse aging, can we keep mice alive indefinitely?
- qup 4y agoMy thought was to take the old mouse, make it young again, and then make it old again. And sure, keep the brother 10 months old forever, but that takes a long time.
- jliptzin 4y agoIt can be like the pitch drop experiment but for mice
- xiphias2 4y agoAubrey de Gray just shared the details a mouse rejuvenation project last week that tests multiple compounds together. It uses 1000 mice, so it costs a lot, but finally there's enough money and data to start the mouse rejuvenation project.
- bilsbie 4y agoDupe https://news.ycombinator.com/item?id=34359964 https://news.ycombinator.com/item?id=34359964
- metadat 4y agoWith one lonely comment. I appreciate if you're trying to be helpful, and hope you'll interpret this unsolicited feedback generously in the constructive spirit it is offered: I didn't find the callout helpful or useful.
- dang 4y agoOn HN, a repost is only considered a dupe if the previous post got significant attention. That may be why users downvoted your comment. https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=by%3Adang%20dupe%20detector%20porous&sort=byDate&type=comment https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que... I know it sucks when your submission was the earlier, overlooked one. We should eventually have some sort of karma-sharing to take care of this. In the meantime, it at least evens out in the long run, since the reason is randomness. https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=by%3Adang%20karma%20sharing&sort=byDate&type=comment https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que...
- senectus1 4y ago"In Mice" really needs to be a Tag or something doesn't it...
- snapplebobapple 4y agoIt is indeed a great time to be a mouse......
- ourmandave 4y agoRight up until your euthanized so they can study your cells and organs under a microscope. =(
- dietr1ch 4y agoOn the Internet nobody knows you are a mouse
- Obscurity4340 4y agoThere's mice on the internet
- KMag 4y agoNo way, half of my diet gives mice cancer! It would stink to be a mouse!
- snapplebobapple 4y agoJust hope you are in group getting the treatment that actually cures that cancer...
- deleted 4y ago[deleted]
- mythhouse 4y agoimplication being they don't transfer over to humans ?
- xiphias2 4y ago,,a loss of epigenetic information is a reversible cause of aging'' While it's probably the most important cause of aging, reversing it may be not enough. Also currently there's no way to prevent cancer cells from being created. ,,Simply titrating the amount of Yamanaka factors that we express, whether by using mRNA, or by having inducible promoters or whatever… these things will stop the mouse or the human from getting teratomas, but I don’t think they’re going to stop them from getting regular cancers, simply because the body of even people your age or my age is already chock-full of cells that have spontaneously accumulated most of the mutations needed to become cancerous.''
- robwwilliams 4y agoIt is not the most important cause of aging. In fact it may be a consequence of aging. There is much more going on during aging then just changes of methylation states.
- kkoncevicius 4y agoWhen you say "just changes in methylation states" it makes it sound as if they don't have any function. Methylation is the mechanism to preserve cell-fate memory after division. Hence in theory it can also carry the information about the "age" of the cell into the daughter cells.
- m3kw9 4y ago[flagged]
- deleted 4y ago[deleted]
- mikesabat 4y agoThe scientist behind the study has both a book and podcast called Lifespan. They are both focused on the epigenetic cause for aging and solutions to slow aging. There are several supplements that the researcher believes will slow aging. The study above is more confirmation of the problem he identified, not a brand new discovery. Cutting to the chase, David Sinclair (the scientist from the article), thinks resveratrol may reverse aging. NAD, which the body produces might also reduce aging. The theory around producing more NAD is that you can actually supplement with the precursor to NAD which is called NMN. If you are really interested, there is an email in my profile. I listened to the entire podcast twice and took a lot of notes. Email me and I will send them.
- zxexz 4y agoThere’s no email in your profile :)
- molticrystal 4y agoDon't see an email, maybe if you (re)add it to the about section of your profile. Please throw them on a google drive or a website or something, I'd love to see an outline/highlights of the state of things by a person who is really interested in the subject.
- layer8 4y ago> Loss of Epigenetic Information Can Drive Aging, Restoration Can Reverse It So… do more backups?
- deleted 4y ago[deleted]
- Rury 4y agoThat alone is not sufficient. Your body makes backups every time it creates a new cell. Once you make a backup of something corrupted, you're going to get corrupted restores. Also, even when you make a non-corrupted backup, it can only be used somewhere around 50-70 times in most cases, and in the few cases where this doesn't apply, well.. you don't want too many copies of them for other reasons (else you get tumors). Lastly, corruption most often happens when you're reading or creating a backup, so simply restoring from a non-corrupted backup might result in corruption. So altogether, doing more backups, won't necessarily solve the problem.
- caseyross 4y agoRather than scrolling through the obligatory endless speculation in the comments, I encourage all of you reading this to open up the section entitled "Long time coming" at the end of the article, and reflect on the fact that worthwhile science is hard and takes a long time to do, and nearly every incentive in academia or industry works in opposition to this. How many other teams could we get working on projects in this field, were it not for funders preferring less risky but far less valuable studies?
- deleted 4y ago[deleted]
- bjornsing 4y agoThis. And more generally: I think a lot that’s wrong with this world stems from the fact that humans are risk averse. This served us well in evolutionary times, when failure often meant death. But in modern societies it causes a lot of problems.
- robwwilliams 4y agoThe NIH and NIA support work of this type reasonably well. And they make risky investments. They have funded our work on aging genetics for 10 years.
- 93po 4y agoIt's sad that we so often have to rely on billionaire's pet projects for work like this. An example being Elon's Neuralink, which from an investment perspective looks like an awful return, but does have insanely high upside if successful.
- xwdv 4y agoWe should run these tests on capybaras.
- grishka 4y agoNo. This whole "aging is the result of loss of something" idea is outdated. The sooner we forget it, the better. Aging is simply the continuation of the development process that starts with conception. It also has to be coordinated across the entire organism somehow so that all tissues and organs age at the same rate, like they do in reality. "There's something in the bloodstream that tells the organism how old it is so it could then act its age" the only plausible explanation for the results of heterochronic parabiosis and other related experiments.
- oneoff786 4y ago> It also has to be coordinated across the entire organism somehow so that all tissues and organs age at the same rate, like they do in reality How could you possibly justify this claim?
- jacobsimon 4y agoI find this theory really interesting, and the fact that it is possible to reverse the epigenetic aging process to the unknown “backup” described in the article would support a mechanism that is coordinated like this rather than random. But it’s possible that the changes are indeed random or probabilistic and that they simply build on each other over time in a way that merely resembles coordinated aging.
- JumpCrisscross 4y ago> No. This whole "aging is the result of loss of something" idea is outdated. The sooner we forget it, the better. This oversimplifies the research. There is strong evidence for programmed death. That doesn't mean there isn't also damage accumulation.
- narrator 4y agoThe superchiasmatic nucleus is probably where the clock that regulates aging is. It's also the clock for everything else in the body though. Just got to tweak that, but maybe that will screw up our feelings of time passing and probably a whole lot of other stuff.
- jkarni 4y agoThis is coming from David Sinclair, who claimed resveratrol was the fountain of youth (it wasn't, but he still managed to sell his resveratrol company for hundreds of millions), and pushed rather hard also on NAD/NMN despite only very preliminary and limited results (he also has interests in NMN companies, and has been involved in removing it from the supplement market in favor of that company's right to market it as a drug). More likely than a cure for aging, Sinclair just found another cure for too few cars in his garage. https://khn.org/news/a-fountain-of-youth-pill-sure-if-youre-a-mouse/ https://khn.org/news/a-fountain-of-youth-pill-sure-if-youre-... https://www.nutraingredients-usa.com/Article/2022/11/15/FDA-s-takedown-of-NMN-raises-fairness-transparency-concerns https://www.nutraingredients-usa.com/Article/2022/11/15/FDA-...
- jjallen 4y agoHe also says this in the article: “ This is the first study showing that we can have precise control of the biological age of a complex animal; that we can drive it forwards and backwards at will” And the paper doesn’t show that at all. The paper does not show them reversing the aging of anything.
- generalizations 4y agoI couldn't get access to the paper, but the abstract and the article both claimed they were able to reverse organ damage caused by the aging. Is that not backed up in the paper?
- ShredKazoo 4y agoWho in the anti-aging space do HN users consider credible?
- robwwilliams 4y agoWithout any doubt—The NIA Interventions Testing Program. They have 20 years of experience on effects of dietary interventions supporting longer lifespan. https://www.nia.nih.gov/research/dab/interventions-testing-program-itp/about-itp https://www.nia.nih.gov/research/dab/interventions-testing-p...
- anovikov 4y agoQuestion must be, have they tried giving the same gene therapy to the "normal" old mice, not artificially aged using ICE? It doesn't prove much if they invented a way to wreck mice' bodies in a pre-designed, controlled way, and then un-wreck them in a way specially tailored to undo that exact kind of damage.
- simne 4y ago> Question must be, have they tried giving the same gene therapy to the "normal" old mice, not artificially aged using ICE? Sure, right scientist MUST make test on control group, which is neutral. This is classics of right science.