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.
more specifically the lack of more failsafes seen in some other mammals are a reaction to something besides happenstance
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.
[0]: https://www.forbes.com/sites/tracybrower/2024/09/15/how-bein...
You can see some of how life might have been like in modern Papua New Guinea. War is nothing like modern warfare with artillery and guns. Its two groups of people firing arrows at each other from stand off distances while shouting at each other with minimal casualties. If you look at casualty rates from some of the early Greek warfare during the hoplite era, it's also surprisingly low.
Also note that in this post, and from research, caloric restriction counteracts some of these inflammatory effects. In many ways modern life can be stressful in its own ways, especially as we remove ourselves more and more from the active lifestyles that necessitated survival in previous eras.
Relevant video by Kurzgesagt – In a Nutshell: https://www.youtube.com/watch?v=Mo1A45ShcMo
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.
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.
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.
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.
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.
Yes, and proteinopathies, and likely lots else besides. We probably don’t even understand the failure modes that aging protects against.
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.
The article about these papers does not present a mechanism that would account for the Hayflick Limit.
Nor does it explain why dogs, for example, age and die more quickly than humans. If there is a mechanism of epigenetic drift that would explain this, I do not see it in the article.
The obvious answer to senescence is that we are programmed to do it. Cells die when they are supposed to die; if they don't, we have a problem.
Likewise, mammals die when they are supposed to. It takes less time to train a puppy to survive on its own than it takes to train a human. Hence, dogs are optimized to age and die more quickly. It's better for the species.
If we were not programmed to get old and die, evolution through natural selection would not work. We would never adapt to changing environments and our species would fail.
Aging and death is not an accident or a deterioration from damage or a drift away from a correct instruction set. It is an absolute hard necessity, without which we would all be long gone.
Stop wasting your time on nonsense articles like this and seek the mechanism that provides us as a species with the flexibility to adapt. Until we see aging and death as an core mechanism, we're going to be looking in the wrong place.