This 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.
“ 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.
I 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?
Without any doubt—The NIA Interventions Testing Program. They have 20 years of experience on effects of dietary interventions supporting longer lifespan.
He is a professor at Harvard - I imagine he wouldn't get to that role if the science didn't have some merit.
Where did he ever say that resveratol was the fountain of youth? Interviews I've seen with him seem more reasonable then I always hear people make him out to be.
NMN does have some promising results based on recent studies- what do you mean he pushed hard? Where did he actually do that?
Andrew Huberman does take and talk about certain medications and supplements which haven't yet been proven effective. However, he has always been completely clear about what the science does and does not say so that people can make up their own minds. He has also consistently been open and ethical about conflicts of interest.
,,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.''
It 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.
When 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.
It 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.
Yes, 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.
The National Institute on Aging has been doing this type of work for 20 years—-but systematically. The NIA Interventions Testing Program is now up to 20,000 mice and many many rational interventional drugs have been tested—-some in combination. The big hit is rapamycin, but there are several orhers.
Looks amazing, thanks! I don't know why it doesn't have more visibility.
I think one of the difference in goals is that interventions testing program repurposes approved drugs, while robust mouse rejuvenation is experimenting with unapproved drugs that have potential to both make mice live longer and translate into humans (thereby having a higher chance of rejuvenating mice)
Both are great and important
projects, I'm just hoping that they fight together instead of against eachother.
Question 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.
Rather 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?
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.
It'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.
> “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.”
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.
My 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.
A 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.
Due 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.
Take that with a high dose of skepticism. Every tissue and cell type has its unique pattern of aging. Epigenetics is a popular but small part of a high dimensional puzzle. Read Steve Austad’s Methuselah’s Zoo if you want wisdom more than headlines.
That 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.
The initial research was done in yeast which was then able to be applied to mice so there is more than a small amount of hope that it will apply to other mammals.
"In mice" is a joke about how misleading it is to omit "in mice" from a study result based on mice. It doesn't make sense to apply it to a headline that does say "in mice", because then it seems to insinuate that mouse research is useless, when in fact countless foundational discoveries have started in mice.
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.
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.
No. 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.
I 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.
The 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.
The 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.
Is 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.
> 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.
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.
DNA 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.
This 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-...
https://www.nutraingredients-usa.com/Article/2022/11/15/FDA-...
He 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.
I 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?
Who in the anti-aging space do HN users consider credible?
Without 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-p...
Does anybody write articles on the stuff that is released from this org that lay people can understand?
There is Reason who runs a successful biotech company, and his corpus of writing at https://fightaging.org
His commentary on new papers in ageing is pretty good, in my opinion.
He has a good coverage of NIA ITP trials as well: https://duckduckgo.com/?q=site%3Afightaging.org+NIA&ia=web
Dr. Kaeberlein and Dr. Attia.
Idk why selling something you believe in disqualifies you as a scientist.
He’s also helped pioneer and make credible the entire field of aging research to reform people’s idea of how to look at aging.
Don’t be so cynical dude.
It's generally still not considered a credible field. Mostly hucksters and grifters.
He is a professor at Harvard - I imagine he wouldn't get to that role if the science didn't have some merit.
Where did he ever say that resveratol was the fountain of youth? Interviews I've seen with him seem more reasonable then I always hear people make him out to be.
NMN does have some promising results based on recent studies- what do you mean he pushed hard? Where did he actually do that?
Resveratrol is "as close to a miraculous molecule as you can find."
NAD+ “is the closest we’ve gotten to a fountain of youth.”
Both quoted in an excellent article on Sinclair:
https://www.bostonmagazine.com/health/2019/10/29/david-sincl...
>> He is a professor at Harvard - I imagine he wouldn't get to that role if the science didn't have some merit.
You should see what Huberman often shills and he's a prestigious professor as well.
Would also add that until recently - and by his own hand - Jordan Peterson was a professor at first Harvard, then the University of Toronto.
what exactly does Huberman shill? As far as I can tell, he has done an extemely commendable service bringing academic literature to the masses.
Don't know about Huberman but how did JP "shill" anything? Can you give a few examples of deceptive statements by him?
> Can you give a few examples of deceptive statements by him?
Joking, are we?
Spill the tea girlfriend, I'm sure you are right but we don't all follow or have even heard of him, why be coy.
He shills diet, sleep and exercise, and maybe circadian stuff. What are you referencing here? The ad sponsors?
Andrew Huberman does take and talk about certain medications and supplements which haven't yet been proven effective. However, he has always been completely clear about what the science does and does not say so that people can make up their own minds. He has also consistently been open and ethical about conflicts of interest.
https://hubermanlab.com/developing-a-rational-approach-to-su...
,,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.''
It 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.
When 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.
It 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.
Yes, 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.
So 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?
My 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.
It can be like the pitch drop experiment but for mice
Aubrey 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.
I assume this is it https://www.lifespan.io/news/aubrey-de-grey-on-levf-and-robu...
Yes
Thanks for the tip nonetheless
The National Institute on Aging has been doing this type of work for 20 years—-but systematically. The NIA Interventions Testing Program is now up to 20,000 mice and many many rational interventional drugs have been tested—-some in combination. The big hit is rapamycin, but there are several orhers.
See: https://www.nia.nih.gov/research/dab/interventions-testing-p...
We published initial genetic results from the first 3500 animals in Science this Sept (2022).
See: https://pubmed.ncbi.nlm.nih.gov/36173858/
Looks amazing, thanks! I don't know why it doesn't have more visibility.
I think one of the difference in goals is that interventions testing program repurposes approved drugs, while robust mouse rejuvenation is experimenting with unapproved drugs that have potential to both make mice live longer and translate into humans (thereby having a higher chance of rejuvenating mice)
Both are great and important projects, I'm just hoping that they fight together instead of against eachother.
Question 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.
> 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.
We should run these tests on capybaras.
Rather 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?
This.
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.
The 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.
It'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.
> “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.
Let's see some 20 year old mice before we get our hopes up.
I'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.
Cheers to getting our hopes up. Hope is pretty cool.
Hopium is a powerful drug
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.
> 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.
My 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.
A 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.
Due 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.
The exact ratio of blame assigned to reasons for increased risk of death over time are still not really settled or universally agreed upon.
Mole rats for example!
Take that with a high dose of skepticism. Every tissue and cell type has its unique pattern of aging. Epigenetics is a popular but small part of a high dimensional puzzle. Read Steve Austad’s Methuselah’s Zoo if you want wisdom more than headlines.
> Loss of Epigenetic Information Can Drive Aging, Restoration Can Reverse It
So… do more backups?
That 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.
"In Mice"
really needs to be a Tag or something doesn't it...
It is indeed a great time to be a mouse......
Right up until your euthanized so they can study your cells and organs under a microscope. =(
On the Internet nobody knows you are a mouse
There's mice on the internet
No way, half of my diet gives mice cancer! It would stink to be a mouse!
Just hope you are in group getting the treatment that actually cures that cancer...
implication being they don't transfer over to humans ?
The initial research was done in yeast which was then able to be applied to mice so there is more than a small amount of hope that it will apply to other mammals.
I just take it as granted that it's going to be in mice until it's explicitly stated 'in humans'
No, it doesn't.
The "in mice" hot take is used to dismiss any new finding without actually contributing anything to the conversation.
"In mice" is a joke about how misleading it is to omit "in mice" from a study result based on mice. It doesn't make sense to apply it to a headline that does say "in mice", because then it seems to insinuate that mouse research is useless, when in fact countless foundational discoveries have started in mice.
Dupe https://news.ycombinator.com/item?id=34359964
With 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.
On 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&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&que...
No. 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.
> 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?
I 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.
> 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.
The 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.
“Study in mice implicates changes to way DNA is organized, regulated rather than changes to genetic code itself”
What??
The 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.
Is 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.
> 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.
This 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.
DNA 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.