With all the mouse research, a lab should compile the top 300 interventions, lifestyles, regimens, etc, and apply it to a generation of mice. Give them all the best of the best gene edits, diets, environments, drug regimens, therapies, exercise, enrichment, and everything else. Get one or two broods of pups each year and breed them for healthspan and well-being, and each year, incorporate the latest and greatest research. Any time they need treatment, or surgery, select from the latest best research for that specific illness or injury.
We have decades of superb mouse health optimization research, it should be applied.
The Interventions Testing Program is the closest thing I know of along these lines.
“ The Interventions Testing Program (ITP) is a peer-reviewed program designed to identify agents that extend lifespan and healthspan in mice. Investigators at any university, institute, company, or other organization are invited to recommend interventions for testing by submitting an application before the February deadline each year. Testing is carried out in the genetically heterogeneous UM-HET3 mouse stock at three sites — the Jackson Laboratory, the University of Michigan, and the University of Texas Health Science Center at San Antonio.”
"Phase 1 clinical trials of a 15-PGDH inhibitor for muscle weakness have shown that it is safe and active in healthy volunteers. Our hope is that a similar trial will be launched soon to test its effect in cartilage regeneration" - Helen Blau, Baxter Laboratory for Stem Cell Biology & the Donald E. and Delia B. Baxter Foundation Professorship
ERa activation promotes PGE2 resulting in decreased 15-PGDH.
So this is one of those standard poor estrogen signaling downstream things and simply improving the estrogen signaling and you get improved cartilage. Anyone can do this today along with getting all of the other positive effects. Those with EDS who have say variants on their TNXA/B have poor production ability to start and so we do everything we can to improve their cartilage production as they can only make so much which include doing stuff like this.
It depends on the person and their genetics. The further you get from the ERa the more complicated this gets and simply stating "Do X" wouldn't apply to everyone even if there are some incredibly common things to do. I might know all the upstream genes, their interactions, and symptoms by heart so it is pretty easy to identify, but general advice would go something like: eat well, get sleep and exercise.
I had microfracture knee surgery. My knee still doesn't feel 100%, and I would love to remain active and keep running. Today, I can do daily work activities, but some physical activities, like running, are painful. I hope this can become a viable solution for humans one day. It would remarkably improve my life.
I’ve had my shoulders “cleaned up” arthroscopically, and the pain is still a major preventer of movement. I would love to stay on the mats longer with something that doesn’t harken to medieval times. So excited at this prospect.
It does get better with physio and exercise. Took me twenty years to recover full (100%) pain-free mobility. It still occasionally finds itself in an uncomfortable spot that can be self-freed, but it can now hold muscle tone across the fascia.
Well, the article notes that it seemed effective on human tissue samples.
The researchers also tested cartilage taken from patients undergoing total knee replacement for osteoarthritis. After one week of treatment with the 15-PGDH inhibitor, the tissue showed fewer 15-PGDH-producing chondrocytes, reduced expression of cartilage degradation and fibrocartilage genes, and early signs of articular cartilage regeneration.
So, IMO that shows hope for once it goes to trials.
Is this available for dogs? I have an aging pup who has early arthritis and I'm considering NAD+ precursor supplements, but this seems much more promising.
A study led by Stanford Medicine researchers has found that an injection blocking a protein linked to aging can reverse the natural loss of knee cartilage in older mice.
If only a small percentage of studies make it past the mice stage to be tested on humans, it means that a lot more studies have been done on mice than humans. Hence, we know more about mouse biology than human biology. So over time, it must get easier and easier to generate positive results in mice, which are uncorrelated with the success in humans.
It's worse than that. People get to interfere in mice. You can stunt their growth, give them transparent skin, grow more or less limbs, cut into them ... you can't experiment at all on humans.
Especially when it comes to pregnancies we know more about a lot of animals than about humans. Why? Well pregnancies is how you multiply meat in animals, which is what farmers are interested in (and pay for). Which ironically also means animal pregnancies can be treated in case of trouble much more effectively.
Why pregnancies? Pregnancy changes a LOT of chemical processes in the body and so quite a bit of "normal" medical knowledge doesn't apply to pregnant women. Which has caused the medical establishment to declare anything that isn't explicitly tested on pregnant women as a no-go zone. So even problems and medications that we do know about, doctors won't apply them to pregnant women.
Yes there are metabolic changes in the mother herself during pregnancy but that's not why it's hard to research. The main fear is that drugs will cross the placenta and affect the growing fetus, or similarly be transmitted through breast milk to an infant. Very young humans are uniquely vulnerable to disruption in their growth that can cause life-long problems.
Would this work for rheumatoid arthritis? I don’t know anything about it myself so it could be a completely different thing, but someone I know has it and it is awful. Would be great to see a treatment coming through.
I’m familiar with Helen Blau, her team is into everything: telomeres and aging, reversing cardiomyopathy, HIV, that team is really hardcore into prolonging and improving lives and wellness.
Heard.
But if even one of their interests panned out it would be paradigm changing for millions and they’re doing it to save your lives not get a updoot on hacker news. They’re all pretty anonymous and understated Imo but i am a great fan and i would love for it to be the “year of” anything they’re studying. I listed a few and I’m sure there’s dozens I’m unaware of.
I’ve been thinking that this stuff is all more closely related than we think and that as they go down one of these paths they’re finding all this other stuff along the way, it’s genuinely fascinating.
Heart disease and failure is one of the biggest ways we meet our ends right now. There’s so much interplay between aging processes, ceasing t-cell production, shortening telomeres , that ties in together with this and im glad they see a bigger picture than me having another 20 years , too winded to stand up and piss or strapped to a bed hooked to tubes and groaning!
Survivor bias of those things that haven't been solved.
Notably absent:
The fat pill
HIV fix
Cystic fibrosis
We make fun of the stuff that hasn't been solved yet ("It's always ten years away!") while ignoring the things that were previously always ten years away until scientists cracked it.
I feel it's unfair to ding Linux on this, even with the implied "slightly less".
I've had Windows as my main personal computer for practically forever, because of games. Before that it was DOS. That changed a couple months ago.
Literally just now--in preparation for this comment--I decided to try something I never tried before: I mounted my Win10 drive, picked an arbitrary old Windows game EXE (2006 "Prey" game demo), and launched it as a "non-Steam game" with just one little drop-down menu tweak... and it launched! I may get 10 FPS instead of 200, but that's more than I expected off the bat.
In the the "years of the Linux desktop" of my youth, I wasn't nearly as optimistic. In terms of more-recent games, I have little reason to keep my old drive for dual-boot purposes except for specific games that go out of their way to interfere with clumsy anti-cheat rootkits.
Back on /. (way back when!) I read an article about optic nerve regrowth in mice. IIRC a lattice was built, stem cells shot onto it, and some other stuff was done, and a new optic nerve ended up growing.
It involved removing the poor mouses existing eye, so there was no net gain (still had a mouse with only 1 working eye), but I was hopeful progress would be made so I could get myself a working optic nerve.
Nope. No progress in 20+ years. Someone got a paper published and went on and did something else.
It is a relatively uncommon problem, for ~98% of children with a problem with their optic nerve, patching the opposite eye works to force the optic nerve to grow. I'm in the (un)lucky 2%!
Admittedly not the worst rare health problem to have.
HN posts about mouse studies always trigger a bunch of skepticism. I’m a layperson so it’s hard to separate the informed comments from me-too contrarians.
Are there areas of medicine where mouse models have a much higher or lower success rate in human trials?
There's two issues, success rate (about 5%) and time ... even if it is successful in humans, it will be 5 to 10 years before it's available (and 20-30 before it's affordable)
To be fair, this same realist perspective seems to suggest humans would not have been capable of developing a COVID vaccine for 5 to 10 years; yet, they identified the virus and authorized vaccine use within eight months.
Not to diminish the accomplishment of rolling out the Covid vaccine in such a rapid timeframe, but… there was something like 40+ years of research into creating mRNA vaccines that laid the ground work.
My dream is to be able to run again. Please. Let me run a 10k at least once more in my life. To feel that stillness and freedom and calm that sets in when the brain start going to hibernation after about 7km.
Check the ElliptiGo. It gives you a similar feeling without the impact on the knees or hip. I know someone who was an avid long life runner. He substituted running for using the ElliptiGo for years and seemed very happy with it. Surprisingly, he was able to run again. I also have the ElliptiGo, but I don't have knee problems, I started using it because at one time I was having neck pain and couldn't run, bike or swim.
Hope you see your dream realized. But know that that stillness is achievable through other activities as well. Most directly and deeply, through a meditation practice which is geared towards reaching those deep meditation states (called Jhanas in the Pali canon). My favorite guide on that particular path is Leigh Brasington.
I broke my ankle nearly two years ago. I've had three surgeries already and will be getting a total ankle replacement in about a month. Even with that, I will never run again.
Sometimes in a dream, I'll start running. I'll notice how magically effortless it feels. How wonderful to be able to run again. Then a little voice in the back of my head reminds me that this can't be real. It wakes me up every time.
It was a rough day when I opened Strava to log one of my physical therapy walks and realized that if I scroll down a bit, I can find a record of the longest run I will ever do.
I'm mostly at peace with it now. I'm grateful that at least I was into running for a while before I lost it, so at least I don't regret never having done it. And I never really enjoyed it then anyway. I just did it for health reasons and the sense of accomplishment.
I'm sorry for your suffering. I know what this longing feels like.
It really sucks when you break something and realise it might not ever go back to how it was before you break it (whether in how it feels or functions). I always had broken bones in my head as this thing that heal after a couple months and you're back to 100% :/ (also broke my ankle)
basically every growth process in the body can be induced by chemicals. and so now people are starting to take some of these chemicals. we will see how it turns out
I had good results with hyaluronic acid for knee osteoarthritis. Sometimes they sell it as Type II Collagen. "Source Naturals Hyaluronic Joint Complex" was the best for my relatives/friends' knee problems. I take it a few times a month (with resveratrol) for smooth skin. I have been taking it since 2008 without any negative result.
Seems like it should work. I do not have experience with that condition. A quick search online (patella tendonitis hyaluronic acid) yielded this study: https://pubmed.ncbi.nlm.nih.gov/22526713/
So they are using hyaluronic acid injections for patella tendonitis. Taking hyaluronic acid orally would probably take longer for effects compared to injections. Most people would prefer the injections because they feel safer for a doctor to do all the work. I prefer the tablets. If you have the money, I guess go for the injections. I would use the H.A. tablets. (With a tall glass of water, and do not take at the same time as blood-thinning medication, like pain killers or drugs.)
You should check out Michael Levin. Cancerous cells do not grow organ-like structures. Normal cells communicate with other cells as a network to control growth.
>Human cartilage samples taken from knee replacement surgeries also responded positively. These samples included both the supportive extracellular matrix of the joint and cartilage-producing chondrocyte cells. When treated, the tissue began forming new, functional cartilage.
Once again, not in humans, in mice. We don't know if the same result happens in humans. At all. We need to proceed to clinical trials to determine if a result is indeed positive.
With all the mouse research, a lab should compile the top 300 interventions, lifestyles, regimens, etc, and apply it to a generation of mice. Give them all the best of the best gene edits, diets, environments, drug regimens, therapies, exercise, enrichment, and everything else. Get one or two broods of pups each year and breed them for healthspan and well-being, and each year, incorporate the latest and greatest research. Any time they need treatment, or surgery, select from the latest best research for that specific illness or injury.
We have decades of superb mouse health optimization research, it should be applied.
The Interventions Testing Program is the closest thing I know of along these lines.
“ The Interventions Testing Program (ITP) is a peer-reviewed program designed to identify agents that extend lifespan and healthspan in mice. Investigators at any university, institute, company, or other organization are invited to recommend interventions for testing by submitting an application before the February deadline each year. Testing is carried out in the genetically heterogeneous UM-HET3 mouse stock at three sites — the Jackson Laboratory, the University of Michigan, and the University of Texas Health Science Center at San Antonio.”
https://www.nia.nih.gov/research/dab/interventions-testing-p...
Is this a joke
paging Bryan Johnson
https://www.science.org/doi/10.1126/science.adx6649
A small molecule inhibitor of 15-hydroxy prostaglandin dehydrogenase causes cartilage regeneration. I hope they fast-track it to human trials.
"Phase 1 clinical trials of a 15-PGDH inhibitor for muscle weakness have shown that it is safe and active in healthy volunteers. Our hope is that a similar trial will be launched soon to test its effect in cartilage regeneration" - Helen Blau, Baxter Laboratory for Stem Cell Biology & the Donald E. and Delia B. Baxter Foundation Professorship
ERa activation promotes PGE2 resulting in decreased 15-PGDH.
So this is one of those standard poor estrogen signaling downstream things and simply improving the estrogen signaling and you get improved cartilage. Anyone can do this today along with getting all of the other positive effects. Those with EDS who have say variants on their TNXA/B have poor production ability to start and so we do everything we can to improve their cartilage production as they can only make so much which include doing stuff like this.
> Anyone can do this today
Please explain
It depends on the person and their genetics. The further you get from the ERa the more complicated this gets and simply stating "Do X" wouldn't apply to everyone even if there are some incredibly common things to do. I might know all the upstream genes, their interactions, and symptoms by heart so it is pretty easy to identify, but general advice would go something like: eat well, get sleep and exercise.
Yes, I deff want this explained, since I'm missing about half of my meniscus.
EDS and arthritis go together so I wonder if we could see secondary effects on other EDS symptoms like subluxation or GI issues?
They already have a human trial in progress...
It is being trialed to prevent muscle weakness and some of those patients will have arthritis and they can be assessed for statistical improvement.
Same thing happened with GLP1
It looks like this enzyme uses NAD+ as a substrate?
I had microfracture knee surgery. My knee still doesn't feel 100%, and I would love to remain active and keep running. Today, I can do daily work activities, but some physical activities, like running, are painful. I hope this can become a viable solution for humans one day. It would remarkably improve my life.
I’ve had my shoulders “cleaned up” arthroscopically, and the pain is still a major preventer of movement. I would love to stay on the mats longer with something that doesn’t harken to medieval times. So excited at this prospect.
It does get better with physio and exercise. Took me twenty years to recover full (100%) pain-free mobility. It still occasionally finds itself in an uncomfortable spot that can be self-freed, but it can now hold muscle tone across the fascia.
Years and years away unfortunately. Many trials and chances for failure on the human side.
It's discouraging to see these on HN and then realize that most never go anywhere, or are so far out you may not see it in your lifetime.
Maybe we should flag anything not already in a phase 3 trial :)
Well, the article notes that it seemed effective on human tissue samples.
So, IMO that shows hope for once it goes to trials.Is this available for dogs? I have an aging pup who has early arthritis and I'm considering NAD+ precursor supplements, but this seems much more promising.
Of course, why are the good ones always in mice?
I guess we should pay scientist to look into the human-to-mice transformation problem
This :))) or the other way around
Are you thinking what I'm thinking?
It's all that wheel running, terrible on the knees.
If only a small percentage of studies make it past the mice stage to be tested on humans, it means that a lot more studies have been done on mice than humans. Hence, we know more about mouse biology than human biology. So over time, it must get easier and easier to generate positive results in mice, which are uncorrelated with the success in humans.
It's worse than that. People get to interfere in mice. You can stunt their growth, give them transparent skin, grow more or less limbs, cut into them ... you can't experiment at all on humans.
Especially when it comes to pregnancies we know more about a lot of animals than about humans. Why? Well pregnancies is how you multiply meat in animals, which is what farmers are interested in (and pay for). Which ironically also means animal pregnancies can be treated in case of trouble much more effectively.
Why pregnancies? Pregnancy changes a LOT of chemical processes in the body and so quite a bit of "normal" medical knowledge doesn't apply to pregnant women. Which has caused the medical establishment to declare anything that isn't explicitly tested on pregnant women as a no-go zone. So even problems and medications that we do know about, doctors won't apply them to pregnant women.
Yes there are metabolic changes in the mother herself during pregnancy but that's not why it's hard to research. The main fear is that drugs will cross the placenta and affect the growing fetus, or similarly be transmitted through breast milk to an infant. Very young humans are uniquely vulnerable to disruption in their growth that can cause life-long problems.
Douglas Adams continues to be ahead of his time.
It's because Mickey Mouse has enough money to fund a lot of medical research, and he's not stingy.
We live in the Matrix, and Mice are the overlords.
"A chemical is something that causes cancer in lab mice."
By analogy, "A drug is something that cures cancer in lab mice."
Would this work for rheumatoid arthritis? I don’t know anything about it myself so it could be a completely different thing, but someone I know has it and it is awful. Would be great to see a treatment coming through.
ra is autoimmune
Fusion Power
Cartilage Regrowth
Room Temperature Semiconductors
Quantum Computing
The only subjects that are more Year Of The Linux Desktop than Linux itself.I’m familiar with Helen Blau, her team is into everything: telomeres and aging, reversing cardiomyopathy, HIV, that team is really hardcore into prolonging and improving lives and wellness.
Heard.
But if even one of their interests panned out it would be paradigm changing for millions and they’re doing it to save your lives not get a updoot on hacker news. They’re all pretty anonymous and understated Imo but i am a great fan and i would love for it to be the “year of” anything they’re studying. I listed a few and I’m sure there’s dozens I’m unaware of.
I’ve been thinking that this stuff is all more closely related than we think and that as they go down one of these paths they’re finding all this other stuff along the way, it’s genuinely fascinating.
Heart disease and failure is one of the biggest ways we meet our ends right now. There’s so much interplay between aging processes, ceasing t-cell production, shortening telomeres , that ties in together with this and im glad they see a bigger picture than me having another 20 years , too winded to stand up and piss or strapped to a bed hooked to tubes and groaning!
Survivor bias of those things that haven't been solved.
Notably absent:
The fat pill HIV fix Cystic fibrosis
We make fun of the stuff that hasn't been solved yet ("It's always ten years away!") while ignoring the things that were previously always ten years away until scientists cracked it.
Also AMT-130 for Huntington's disease.
>Year Of The Linux Desktop
After Win11 Microsoft really did all they could to get us there this year.
I think 'room temperature semiconductors' have been around for a while.
Not if Intel has anything to say about it!
I feel it's unfair to ding Linux on this, even with the implied "slightly less".
I've had Windows as my main personal computer for practically forever, because of games. Before that it was DOS. That changed a couple months ago.
Literally just now--in preparation for this comment--I decided to try something I never tried before: I mounted my Win10 drive, picked an arbitrary old Windows game EXE (2006 "Prey" game demo), and launched it as a "non-Steam game" with just one little drop-down menu tweak... and it launched! I may get 10 FPS instead of 200, but that's more than I expected off the bat.
In the the "years of the Linux desktop" of my youth, I wasn't nearly as optimistic. In terms of more-recent games, I have little reason to keep my old drive for dual-boot purposes except for specific games that go out of their way to interfere with clumsy anti-cheat rootkits.
Don't forget about Alzheimer's disease
Back on /. (way back when!) I read an article about optic nerve regrowth in mice. IIRC a lattice was built, stem cells shot onto it, and some other stuff was done, and a new optic nerve ended up growing.
It involved removing the poor mouses existing eye, so there was no net gain (still had a mouse with only 1 working eye), but I was hopeful progress would be made so I could get myself a working optic nerve.
Nope. No progress in 20+ years. Someone got a paper published and went on and did something else.
It is a relatively uncommon problem, for ~98% of children with a problem with their optic nerve, patching the opposite eye works to force the optic nerve to grow. I'm in the (un)lucky 2%!
Admittedly not the worst rare health problem to have.
Battery tech
Blockchain & DeFi!
Bingo!
:-D
https://www.sciencedirect.com/science/article/abs/pii/S01637...
Reduce arthritis, get cancer?
Pioglitazone does this now. It is sometimes used for diabetes.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11862886/
HN posts about mouse studies always trigger a bunch of skepticism. I’m a layperson so it’s hard to separate the informed comments from me-too contrarians.
Are there areas of medicine where mouse models have a much higher or lower success rate in human trials?
There's two issues, success rate (about 5%) and time ... even if it is successful in humans, it will be 5 to 10 years before it's available (and 20-30 before it's affordable)
This is not being a contrarian, but a realist.
To be fair, this same realist perspective seems to suggest humans would not have been capable of developing a COVID vaccine for 5 to 10 years; yet, they identified the virus and authorized vaccine use within eight months.
Not to diminish the accomplishment of rolling out the Covid vaccine in such a rapid timeframe, but… there was something like 40+ years of research into creating mRNA vaccines that laid the ground work.
> and 20-30 before it's affordable
Not if pharma execs and shareholders have anything to say about that
It has also been tested in cartilage samples from knee replacement surgeries.
My dream is to be able to run again. Please. Let me run a 10k at least once more in my life. To feel that stillness and freedom and calm that sets in when the brain start going to hibernation after about 7km.
That would be quiet something to feel that again.
Check the ElliptiGo. It gives you a similar feeling without the impact on the knees or hip. I know someone who was an avid long life runner. He substituted running for using the ElliptiGo for years and seemed very happy with it. Surprisingly, he was able to run again. I also have the ElliptiGo, but I don't have knee problems, I started using it because at one time I was having neck pain and couldn't run, bike or swim.
Hope you see your dream realized. But know that that stillness is achievable through other activities as well. Most directly and deeply, through a meditation practice which is geared towards reaching those deep meditation states (called Jhanas in the Pali canon). My favorite guide on that particular path is Leigh Brasington.
I broke my ankle nearly two years ago. I've had three surgeries already and will be getting a total ankle replacement in about a month. Even with that, I will never run again.
Sometimes in a dream, I'll start running. I'll notice how magically effortless it feels. How wonderful to be able to run again. Then a little voice in the back of my head reminds me that this can't be real. It wakes me up every time.
It was a rough day when I opened Strava to log one of my physical therapy walks and realized that if I scroll down a bit, I can find a record of the longest run I will ever do.
I'm mostly at peace with it now. I'm grateful that at least I was into running for a while before I lost it, so at least I don't regret never having done it. And I never really enjoyed it then anyway. I just did it for health reasons and the sense of accomplishment.
I'm sorry for your suffering. I know what this longing feels like.
Godamn that sucks :(. What did you do to it?
It really sucks when you break something and realise it might not ever go back to how it was before you break it (whether in how it feels or functions). I always had broken bones in my head as this thing that heal after a couple months and you're back to 100% :/ (also broke my ankle)
Can you swim? This is the only thing besides running that gets me there.
A Concept 2 rowing machine can also do this (in my experience). No impact, similar to swimming.
basically every growth process in the body can be induced by chemicals. and so now people are starting to take some of these chemicals. we will see how it turns out
As long as regrowth can be controlled. Otherwise we call it cancer. Would be amazing to get a treatment for osteoarthritis.
I had good results with hyaluronic acid for knee osteoarthritis. Sometimes they sell it as Type II Collagen. "Source Naturals Hyaluronic Joint Complex" was the best for my relatives/friends' knee problems. I take it a few times a month (with resveratrol) for smooth skin. I have been taking it since 2008 without any negative result.
How does Type II Collagen work for patella tendonitis? I have jumpers knee (chronic) and would love to find something that helps -- even a little.
Seems like it should work. I do not have experience with that condition. A quick search online (patella tendonitis hyaluronic acid) yielded this study: https://pubmed.ncbi.nlm.nih.gov/22526713/
So they are using hyaluronic acid injections for patella tendonitis. Taking hyaluronic acid orally would probably take longer for effects compared to injections. Most people would prefer the injections because they feel safer for a doctor to do all the work. I prefer the tablets. If you have the money, I guess go for the injections. I would use the H.A. tablets. (With a tall glass of water, and do not take at the same time as blood-thinning medication, like pain killers or drugs.)
You should check out Michael Levin. Cancerous cells do not grow organ-like structures. Normal cells communicate with other cells as a network to control growth.
>Human cartilage samples taken from knee replacement surgeries also responded positively. These samples included both the supportive extracellular matrix of the joint and cartilage-producing chondrocyte cells. When treated, the tissue began forming new, functional cartilage.
Once again, not in humans, in mice. We don't know if the same result happens in humans. At all. We need to proceed to clinical trials to determine if a result is indeed positive.
Ok, we've inmiced the title above. Thanks!
No, it's in humans. It's literally the first sentence in your quote.
The discovery of gerozymes is interesting. Maybe aging is pre-programmed after all, to make space for new generations.