This particular paper was funded by the National Natural Science Foundation of China, along with various other Chinese organizations. China's biology/biotech research is top-tier, these days, and the Chinese government actively funds quite a lot of basic research in the life sciences. Interestingly, very little of it seems to translate to in-country pharmaceutical development.
When was the last time you heard of a Chinese pharmaceutical company with a novel, non-generic product?
Sure, the Chinese make existing drugs and APIs. They're probably the world leaders in generic peptide production. They also do a lot of basic research. What is lacking -- what is proportionately small -- is their share of innovative new drugs developed. This is slowly changing, but the Chinese are way behind in drug development and commercialization. That's what I meant.
Open a journal, sample a bunch of articles. Usually, there's an acknowledgement (sometimes in the first footnote) with the program that funded the research. If there is none, it's possibly a regular, university funded project, in which case you'd have to look up the uni's funding.
Basically, the authors were able to treat progeria (to some extent) by designing a peptide which prevented progerin (the characteristic progeria protein) from binding with the ubiquitous cellular regulator protein BUBR1.
It has been known for about 20 years that BUBR1 irregularities can be associated with early-onset aging phenotypes: https://www.nature.com/articles/ng1382
Loads, but it's still hard to tell which of them are (1) more than just statistical anomalies, (2) aren't limited to in vitro/in muribus, and (3) don't have "cause cancer" as a side effect.
Some Hollywood stars do a lot of that. Most people just don't get excited at messages to live right every day for decades. They want to eat like pigs, smoke, drink and do drugs and then get a pill or surgery that dramatically repairs it practically overnight.
Aging is a set of effects, in one sense of course it’s not aging if the time hasn’t actually passed but it seems that some of the same effects are happening.
What do you think aging is? I was under the impression that there is evidence that aging is due to degradation of cell DNA over time, even if this isn't known conclusively at this time.
My impression is that all the aging talk the last several years seems to have been centered around epigenetics, senescent cells, other topics aside from just DNA mutations.
It is funny to wonder how it is that people who aren't in their prime youth anymore, who already have visible signs of aging, are able to have a baby who will get a fresh start, with intact DNA. It is like there is a complete reset button on aging. Your cells know how to replicate themselves without inheriting the accumulated damage, or any of the markers of aging.
The parent cells do accumulate mutations, and with it an increased risk of cancer. But as soon as the reset switch is hit, we start back at zero. In the embryo, telomeres are long again, and cancer risk is low. Everywhere else in the parent's cells, aging continues unabated.
If aging is DNA degradation, isn't it weird how aging isn't inherited?
> It is funny to wonder how it is that people who aren't in their prime youth anymore, who already have visible signs of aging, are able to have a baby who will get a fresh start, with intact DNA. It is like there is a complete reset button on aging.
My understanding is that this is one of primary purposes of gametes (eggs and sperm). That the body does have the ability to repair DNA (the testes do this during sperm production), but that it's very energy intensive. It does make sense that from an evolutionary perspective, individuals living longer may not actually contribute (and may actually be a detriment) to species fitness past a certain point.
If a near-perfect repair capability were available, I can't see that it would be very costly to the body to, for instance, use it on stem cells, progenitor cells, any -blast sufficiently up the hierarchy. I can't see it being all that energy intensive. It seems to me that DNA manipulation is relatively efficient, double-stranded break repairs via homologous recombination or NHEJ is in every cell. Bread and butter for your skin cells.
And surely the energy consumption of all the turnover in epidermal cells alone would vastly overshadows the hypothetical cost of DNA repair in -blasts? We further spend serious amounts of energy on the immune system, on the brain, on all sorts of things, and we have good energy regulation mechanisms. Compared to all the things the body already does, spending energy on DNA repair seems like an excellent trade, when not actively underfed.
I'm also suspicious of the argument that individuals living longer would be a detriment. DNA repair would not just cause longer life in the sense of very old people sticking around longer. It'd mean individuals living healthier lives for longer, so that they may still contribute to society, take care of grandkids, etc. Raising children is a big cost. If people lived longer healthy lives, arguably they could afford to have kids later if they chose to, which I imagine would save resources (e.g. by having a smaller percentage of life being spent in infancy and growth), potentially increasing fitness?
A different argument still is that the body seems to have evolved many mechanisms to prevent cancer and to fight it when it happens. It seems that there has been selection pressure in the direction against DNA damage being a cause of death.
If there were fitness in making people live shorter lives, I'd expect the body to try to do this not by letting DNA damage accumulate, but by trying to keep people as healthy as possible during their life, then separately using a programmed end-of-life to enforce a limit. I can't find the reason why this would be significantly hard for evolution to come up with, aside from the pristine DNA repair mechanism actually existing as described, which I don't think is really the case, no?
Aging isn't inherited? Older women's eggs make more children who are more likely to be retarded. Older men's make more children who more likely are taller, more prone to obesity, and schizophrenic.
You don't start at zero. If your parents aren't healthy you likely won't be either. If you parents have undamaged eggs or sperm youll inherit more of your grandfathers traits from the x chromosome. If not you'll get my father's mutations.
That's true to an extent, yes. Hoewer if aging were inherited in a meaningful sense, the species would not have survived very long.
My point behind this is that DNA mutations are normally inherited, and indeed we also see that older parents' children have higher risk. But that aging still almost entirely resets suggest that most of the effects of aging are not just plain DNA mutations. Hence the idea that it must be mainly something else that is not inherited, like epigenetics, senescent cells, etc
We know it's not just DNA mutations, but you're conflating that with curing aging. More intelligent octopuses live for shorter periods of time, as do cuttlefish. The gene makes them intelligent as well as die sooner. Their species doesn't need long lifespans and it also isn't aging unnaturally long.
Humans can age longer because they delay death at the cost of their genetic coding. Unless you're stopping this sooner rather than later it will be for nothing. Unfortunately the person I considered an expert on this is now blacklisted. He was more interested in reversing aging rather than delaying these effects, by removing all the mitochondria. Have you looked into the mitomouse?
Aging is one side effect of a major internal system that counteracts cancers.
Most of our cells are preprogrammed to die after a certain number of replications. This is one of many systems that counteract normal genetic mutations - which can cause cancers and other side effects. By definition a cancer has to reproduce and one way of defeating cancers is for cells to die (or be killed) once they reach a number of cell reproductions.
Think of a binary tree where the tree depth is the number of cell reproductions, and telomere length controls tree depth. Each time a cell reproduces it risks mutations. Stem cells are the progenitor branches, and stem cells maintain “cleaner” copies of DNA, which then become normal cells. Normal cells then reproduce a number of times before they kill themselves.
We have evolved this system because it balances the shorter term harms of cancer (high cost preventing reproduction), and senescence (lower cost after reproduction).
There can be no “cure” for cancer, or aging. The cure would for cancer would require some way to either cause perfect cell reproduction, or to remove (or correct) all cells with imperfect reproductions. The “cure” for aging would require a cure for cancer. If I were to invest in something myself, it would be brain transplant, since brain cancers are rare, and dealing with organ rejection seems doable, and the issue of nerve reconnection seems solvable. The main problem is finding spare bodies, which can be unethically solved for a few wealthy people.
Good questions for sure. The answer is probably "it depends", but knowing what we know about how gut is connected with the mind swapping it out probably is much more drastic than a mild head injury or taking some drugs.
Brain transplants are no good because most normal humans would be psychologically be scarred from this.
In a fantastic world there would be self duplication and maybe transport your brain in your own dupe. There is no other way that after such transplant you wouldn’t suffer a fate worse than death, and so will your loved ones
This horrible disease touched my extended family. Unfortunately, rare 'orphan' diseases are under-funded because there aren't enough patients to make them profitable. More Pharma shareholder value with yet another drug that appears to have a slight statistical effect on Alzheimer's than with a full cure for progeria.
Unfortunately, rare 'orphan' diseases are under-funded because there aren't enough patients to make them profitable.
"Minor" (cough) flaw in our so-called healthcare system.
I don't know how to fix it, sadly. But, wow, is this "your money or your life" medical system not exactly optimizing for positive health outcomes for the people.
This is conspiracy theory. The US does fund a lot of research into rare diseases, which would never be economical to research otherwise. There are only so many dollars to go around, obviously, and research into common diseases has the potential to help more people.
If anything, research into effective treatments for common diseases is underfunded.
It’s obviously bad news to have a rare disease, but it’s frankly astounding that we still don’t have rock solid effective knowledge* for how to maintain effective diets.
* “Move more eat less” or CICO don’t count since people have been saying this forever, people have been attempting it forever, and people fail at it at extremely high rates, so it’s definitionally not effective.
Long time ago I read one of the predictions, cannot remember who, and one of the lines was saying "World will struck illness of rapid aging", at the time it looks so silly, but after reading this it looks so odd...
After Covid and CRISPER advances, I wonder how far is future where someone come up with idea to weaponize this finding or just try a test that will go wrong and escaping lab. Well, I hope not ...
And you would be wrong: diseases which kill die out. Diseases which do not kill spread far and wide: COVID is successful and dangerous precisely because it mostly doesn't kill, and it keeps you on your feet and contagious for a good long time.
They wouldn't need to kill many. Just a few around the world to scare everyone. Heard the DC sniper terrorized people over a longer period but didn't kill that many.
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[ 0.24 ms ] story [ 114 ms ] threadSure, the Chinese make existing drugs and APIs. They're probably the world leaders in generic peptide production. They also do a lot of basic research. What is lacking -- what is proportionately small -- is their share of innovative new drugs developed. This is slowly changing, but the Chinese are way behind in drug development and commercialization. That's what I meant.
E.g., for this article: https://www.nature.com/articles/s43587-023-00361-w#Ack1
Basically, the authors were able to treat progeria (to some extent) by designing a peptide which prevented progerin (the characteristic progeria protein) from binding with the ubiquitous cellular regulator protein BUBR1.
It has been known for about 20 years that BUBR1 irregularities can be associated with early-onset aging phenotypes: https://www.nature.com/articles/ng1382
Some Hollywood stars do a lot of that. Most people just don't get excited at messages to live right every day for decades. They want to eat like pigs, smoke, drink and do drugs and then get a pill or surgery that dramatically repairs it practically overnight.
Diseases that have to do with "failure to follow the genetic plan [...]" are much more worse than aging, you don't even get to age!
This is not aging. That's the point I'm making.
It is funny to wonder how it is that people who aren't in their prime youth anymore, who already have visible signs of aging, are able to have a baby who will get a fresh start, with intact DNA. It is like there is a complete reset button on aging. Your cells know how to replicate themselves without inheriting the accumulated damage, or any of the markers of aging.
The parent cells do accumulate mutations, and with it an increased risk of cancer. But as soon as the reset switch is hit, we start back at zero. In the embryo, telomeres are long again, and cancer risk is low. Everywhere else in the parent's cells, aging continues unabated.
If aging is DNA degradation, isn't it weird how aging isn't inherited?
My understanding is that this is one of primary purposes of gametes (eggs and sperm). That the body does have the ability to repair DNA (the testes do this during sperm production), but that it's very energy intensive. It does make sense that from an evolutionary perspective, individuals living longer may not actually contribute (and may actually be a detriment) to species fitness past a certain point.
I'm also suspicious of the argument that individuals living longer would be a detriment. DNA repair would not just cause longer life in the sense of very old people sticking around longer. It'd mean individuals living healthier lives for longer, so that they may still contribute to society, take care of grandkids, etc. Raising children is a big cost. If people lived longer healthy lives, arguably they could afford to have kids later if they chose to, which I imagine would save resources (e.g. by having a smaller percentage of life being spent in infancy and growth), potentially increasing fitness?
A different argument still is that the body seems to have evolved many mechanisms to prevent cancer and to fight it when it happens. It seems that there has been selection pressure in the direction against DNA damage being a cause of death. If there were fitness in making people live shorter lives, I'd expect the body to try to do this not by letting DNA damage accumulate, but by trying to keep people as healthy as possible during their life, then separately using a programmed end-of-life to enforce a limit. I can't find the reason why this would be significantly hard for evolution to come up with, aside from the pristine DNA repair mechanism actually existing as described, which I don't think is really the case, no?
You don't start at zero. If your parents aren't healthy you likely won't be either. If you parents have undamaged eggs or sperm youll inherit more of your grandfathers traits from the x chromosome. If not you'll get my father's mutations.
My point behind this is that DNA mutations are normally inherited, and indeed we also see that older parents' children have higher risk. But that aging still almost entirely resets suggest that most of the effects of aging are not just plain DNA mutations. Hence the idea that it must be mainly something else that is not inherited, like epigenetics, senescent cells, etc
Humans can age longer because they delay death at the cost of their genetic coding. Unless you're stopping this sooner rather than later it will be for nothing. Unfortunately the person I considered an expert on this is now blacklisted. He was more interested in reversing aging rather than delaying these effects, by removing all the mitochondria. Have you looked into the mitomouse?
Our body has some mechanisms to cope with that but they're not perfect, those residual issues + time is aging, IMO.
Most of our cells are preprogrammed to die after a certain number of replications. This is one of many systems that counteract normal genetic mutations - which can cause cancers and other side effects. By definition a cancer has to reproduce and one way of defeating cancers is for cells to die (or be killed) once they reach a number of cell reproductions.
Think of a binary tree where the tree depth is the number of cell reproductions, and telomere length controls tree depth. Each time a cell reproduces it risks mutations. Stem cells are the progenitor branches, and stem cells maintain “cleaner” copies of DNA, which then become normal cells. Normal cells then reproduce a number of times before they kill themselves.
We have evolved this system because it balances the shorter term harms of cancer (high cost preventing reproduction), and senescence (lower cost after reproduction).
There can be no “cure” for cancer, or aging. The cure would for cancer would require some way to either cause perfect cell reproduction, or to remove (or correct) all cells with imperfect reproductions. The “cure” for aging would require a cure for cancer. If I were to invest in something myself, it would be brain transplant, since brain cancers are rare, and dealing with organ rejection seems doable, and the issue of nerve reconnection seems solvable. The main problem is finding spare bodies, which can be unethically solved for a few wealthy people.
The balanced-tree-depth metaphor makes me think of this: https://m.youtube.com/watch?v=plVk4NVIUh8 although admittedly it isn’t that relevant!
Disclaimer: not a biologist.
In a fantastic world there would be self duplication and maybe transport your brain in your own dupe. There is no other way that after such transplant you wouldn’t suffer a fate worse than death, and so will your loved ones
I think it's a mistake to assume that some treatment for progeria would be a treatment for aging in healthy humans.
"Minor" (cough) flaw in our so-called healthcare system.
I don't know how to fix it, sadly. But, wow, is this "your money or your life" medical system not exactly optimizing for positive health outcomes for the people.
It’s obviously bad news to have a rare disease, but it’s frankly astounding that we still don’t have rock solid effective knowledge* for how to maintain effective diets.
* “Move more eat less” or CICO don’t count since people have been saying this forever, people have been attempting it forever, and people fail at it at extremely high rates, so it’s definitionally not effective.
That's not true. Genzyme (acquired by Sanofi for $20B) has a whole portfolio of orphan disease drugs, they do nothing else.
The success of rare disease drugs actually inspired a lot of big pharma to get into it too.