> Do we currently have the ability to do targeted methylation or de methylation at sites in cells?
No, and you probably wouldn’t want it if you could. You don’t know what mutations are lurking in the genes that have been switched off or the consequences of turning them back on.
I’ve thought about this a bit, and what resetting the methylation map really requires, in addition to actually resetting that map, is resetting your genome to a known good state.
That’s pretty radical, but to selectively switch methylation on and off with precision you’re already talking about science beyond anything we have, featuring custom engineered constellations of proteins that unwrap your chromatin from around histones and then walk along it changing methylation state, then pack everything back.
And doing it for each cell type, without applying the wrong map anywhere.
And knowing what all the cell types and their correct methylation maps actually are.
And assuming that methylation isn’t used anywhere, for example in the brain, in a way we don’t expect.
And methylation isn’t the only kind of epigenetic modification.
So, if we’ve solved all of those problems, rebuilding your DNA to a clean, mutation free state at the same time should be a breeze.
We really do need AI for this if any of it is going to be remotely feasible.
Cancer is the price we pay for complex multicellular life. It’s not a failsafe, it’s the failure of all failsafes to regulate cellular growth within an organism.
> We really do need AI for this if any of it is going to be remotely feasible.
Would you give your life into the hands of AI skynet slop?
I understand your rationale, of course, but I for one don't want big fat mega-corporations dictate over our life here. Naturally, all of this hinges whether AI can even solve this problem. I assume it can, but I doubt it can do so initially - and the legal implications are still enormous. I really am not ready to turn my hands to claude's gene therapy slop.
It makes me concerned on many levels, but perhaps also more hopeful. It was inevitable that we would eventually develop AI if we didn't go extinct first, and while there are myriad risks and challenges, there is also massive potential, which seems like it could be a source of hope. As the earlier comment said, the only way that therapies like these could be remotely viable on any kind of near to medium timeframe would be with AI assistance, and this is just one example.
What about Xanax or medication. Hypothetically ignoring the ill effects of the drugs themselves will chemical stress relief have the same anti-aging benefits?
I just don't understand. Wouldn't we have evolved in an environment with constant stress? Constant fear of disease, starvation, predation, attacks by neighboring tribes? Why would our body's natural response to our environment be to immediately grenade itself.
I suppose the stress was running away from a lion, not having the all-eating thought of meeting deadlines, a bad boss, backstabbing coworkers and so on, i.e. intense, but short, not persistent and chronic.
I'm no biologist, but it's pretty easy to imagine a plausible mechanism.
Stress doesn't cause your body to "immediately grenade itself", it causes gradual problems over an extended period. But you can imagine that evolutionarily speaking, a stressful situation would frequently be a situation involving imminent danger. A response that prioritizes short-term survival (e.g. releasing adrenaline and cortisol) regardless of the long-term consequences could easily improve evolutionary fitness.
Considering that aging only happens later in life, it wouldn't have much of an effect on how efficient humans produce offspring, so it wouldn't be selected against. It is the same explanation for why Huntington's and Alzheimer's are still around.
> Wouldn't we have evolved in an environment with constant stress?
Well, humans did not reach an old age if you look back to history.
Only in recent times, say, 2000 years or so, or, if you want to be
strict, the last 100 years, did humans reach very old ages. Back
in older days, 30 years was considered old. Then 40 or so.
I suspect that epigenetic aging is adaptive; a deliberately programmed sequence wherein genes more likely to contribute to age-related mortality are shut down progressively. This being in response to random genetic damage accumulating at a predictable rate.
What we think of as aging then becomes primarily the epigenetic response to the problem of DNA damage, much like the symptoms of a virus are mostly the result of the immune response rather than the virus’s direct effects.
Can you state which genes these are that do that? Because I don't know of any.
Plus, many genes have pleiotropic effects. There is no specific aging gene.
On top of that, aging is a word that combines to many different factors. For
instance, progeria was called accelerated aging. Well, turns out you have a
mutation in lamin A. So, it is about cytoskeletal structure that is defect, rather than aging in itself. Of course the effects that this has, looks like an older person then, so it is related to aging. But one can not say it is "accelerated aging" as such. People having a normal lamin A allele still age nonetheless. So the whole term is problematic. And you can find many more such descriptions where xyz is about aging. Well, most of that it is about damage rather than aging. The Hayflick limit, though, is not about damage; that's just that cells fatigue for some reason when their telomeres shorten, but I have not yet read a sound explanations about why that is the case - after all there must be a mechanism in place.
There's a lot of indirect evidence for this from the fact that some naive attempts at stopping aging give you cancer, like turning telomerase on indiscriminately.
Almost everything in nature has multiple functions or causes, but one cause of aging is probably an evolutionary compromise between longevity and not getting cancer.
One option, I guess, would be turning the guard rails off and just getting incredibly good at treating cancer or inventing some extraneous cancer detection and killing mechanism.
It’s rarely such a simple tradeoff that only two things are being optimized. Modern humans live way longer than wolves for example despite being of similar body mass. However that’s fairly new in our evolutionary history as wild chimps for example cap our at ~63.
Cancer is extremely rare as a cause of death in wild animals. Again is more common but late enough that reproduction has produced multiple offspring.
Energy expenditure isn’t something we’re concerned with but drives a great deal of evolutionary optimization.
The two papers:
* https://www.nature.com/articles/s41586-026-10955-0
* https://www.cell.com/cell/abstract/S0092-8674(25)00853-0
So chronic stress is one of the main contributors to aging. I hope I make it to my 40s.
Do we currently have the ability to do targeted methylation or de methylation at sites in cells?
> Do we currently have the ability to do targeted methylation or de methylation at sites in cells?
No, and you probably wouldn’t want it if you could. You don’t know what mutations are lurking in the genes that have been switched off or the consequences of turning them back on.
I’ve thought about this a bit, and what resetting the methylation map really requires, in addition to actually resetting that map, is resetting your genome to a known good state.
That’s pretty radical, but to selectively switch methylation on and off with precision you’re already talking about science beyond anything we have, featuring custom engineered constellations of proteins that unwrap your chromatin from around histones and then walk along it changing methylation state, then pack everything back.
And doing it for each cell type, without applying the wrong map anywhere.
And knowing what all the cell types and their correct methylation maps actually are.
And assuming that methylation isn’t used anywhere, for example in the brain, in a way we don’t expect.
And methylation isn’t the only kind of epigenetic modification.
So, if we’ve solved all of those problems, rebuilding your DNA to a clean, mutation free state at the same time should be a breeze.
We really do need AI for this if any of it is going to be remotely feasible.
in my futile searches for meaning I’ve wondered whether cancers in humans are a failsafe to something else or preventing something worse
more specifically the lack of more failsafes seen in some other mammals are a reaction to something besides happenstance
Cancer is the price we pay for complex multicellular life. It’s not a failsafe, it’s the failure of all failsafes to regulate cellular growth within an organism.
> We really do need AI for this if any of it is going to be remotely feasible.
Would you give your life into the hands of AI skynet slop?
I understand your rationale, of course, but I for one don't want big fat mega-corporations dictate over our life here. Naturally, all of this hinges whether AI can even solve this problem. I assume it can, but I doubt it can do so initially - and the legal implications are still enormous. I really am not ready to turn my hands to claude's gene therapy slop.
Good news! Research shows that hope reduces stress! [0]
[0]: https://www.forbes.com/sites/tracybrower/2024/09/15/how-bein...
Sometimes I like to close my eyes and dream of electric sheep.
Sadly, AI just made many of us lose all hope.
It makes me concerned on many levels, but perhaps also more hopeful. It was inevitable that we would eventually develop AI if we didn't go extinct first, and while there are myriad risks and challenges, there is also massive potential, which seems like it could be a source of hope. As the earlier comment said, the only way that therapies like these could be remotely viable on any kind of near to medium timeframe would be with AI assistance, and this is just one example.
You spelled SI wrong.
Thanks, Obama
What about Xanax or medication. Hypothetically ignoring the ill effects of the drugs themselves will chemical stress relief have the same anti-aging benefits?
If you believe that HRV is inversely correlated with stress then Xanax has the opposite of your intended effect.
I just don't understand. Wouldn't we have evolved in an environment with constant stress? Constant fear of disease, starvation, predation, attacks by neighboring tribes? Why would our body's natural response to our environment be to immediately grenade itself.
I suppose the stress was running away from a lion, not having the all-eating thought of meeting deadlines, a bad boss, backstabbing coworkers and so on, i.e. intense, but short, not persistent and chronic.
There always has been a lot of stress, but there used to be relaxed moments as well. The issue is that we don't calm down anymore.
Relevant video by Kurzgesagt – In a Nutshell: https://www.youtube.com/watch?v=Mo1A45ShcMo
I'm no biologist, but it's pretty easy to imagine a plausible mechanism.
Stress doesn't cause your body to "immediately grenade itself", it causes gradual problems over an extended period. But you can imagine that evolutionarily speaking, a stressful situation would frequently be a situation involving imminent danger. A response that prioritizes short-term survival (e.g. releasing adrenaline and cortisol) regardless of the long-term consequences could easily improve evolutionary fitness.
Considering that aging only happens later in life, it wouldn't have much of an effect on how efficient humans produce offspring, so it wouldn't be selected against. It is the same explanation for why Huntington's and Alzheimer's are still around.
> Considering that aging only happens later in life,
In other news, widows outlive their husbands.
> Wouldn't we have evolved in an environment with constant stress?
Well, humans did not reach an old age if you look back to history. Only in recent times, say, 2000 years or so, or, if you want to be strict, the last 100 years, did humans reach very old ages. Back in older days, 30 years was considered old. Then 40 or so.
I suspect that epigenetic aging is adaptive; a deliberately programmed sequence wherein genes more likely to contribute to age-related mortality are shut down progressively. This being in response to random genetic damage accumulating at a predictable rate.
What we think of as aging then becomes primarily the epigenetic response to the problem of DNA damage, much like the symptoms of a virus are mostly the result of the immune response rather than the virus’s direct effects.
This assumes there are genes that:
a) contribute to age-related mortality, and
b) shutting down helps combat aging.
Can you state which genes these are that do that? Because I don't know of any.
Plus, many genes have pleiotropic effects. There is no specific aging gene.
On top of that, aging is a word that combines to many different factors. For instance, progeria was called accelerated aging. Well, turns out you have a mutation in lamin A. So, it is about cytoskeletal structure that is defect, rather than aging in itself. Of course the effects that this has, looks like an older person then, so it is related to aging. But one can not say it is "accelerated aging" as such. People having a normal lamin A allele still age nonetheless. So the whole term is problematic. And you can find many more such descriptions where xyz is about aging. Well, most of that it is about damage rather than aging. The Hayflick limit, though, is not about damage; that's just that cells fatigue for some reason when their telomeres shorten, but I have not yet read a sound explanations about why that is the case - after all there must be a mechanism in place.
There's a lot of indirect evidence for this from the fact that some naive attempts at stopping aging give you cancer, like turning telomerase on indiscriminately.
Almost everything in nature has multiple functions or causes, but one cause of aging is probably an evolutionary compromise between longevity and not getting cancer.
One option, I guess, would be turning the guard rails off and just getting incredibly good at treating cancer or inventing some extraneous cancer detection and killing mechanism.
It’s rarely such a simple tradeoff that only two things are being optimized. Modern humans live way longer than wolves for example despite being of similar body mass. However that’s fairly new in our evolutionary history as wild chimps for example cap our at ~63.
Cancer is extremely rare as a cause of death in wild animals. Again is more common but late enough that reproduction has produced multiple offspring.
Energy expenditure isn’t something we’re concerned with but drives a great deal of evolutionary optimization.
> one cause of aging is probably an evolutionary compromise between longevity and not getting cancer
Yes, and proteinopathies, and likely lots else besides. We probably don’t even understand the failure modes that aging protects against.