5 ms·

The usual caveat applies: > Does it work? It does and it works quite well. Tests have shown that the preparation developed by the scientists forced the product

The usual caveat applies: > Does it work? It does and it works quite well. Tests have shown that the preparation developed by the scientists forced the production of antibodies in the bodies of mice, which through the white blood cells attacked the aging cells in their bodies. The average lifespan of laboratory rodents that took the preparation extended by 15 percent relative to the control group, and individuals suffering from arterial stiffness saw a significant reduction in the damaged areas of these blood vessels. Results in mice will probably not track to humans, assuming this treatment even makes it to that stage. The development time for most vaccines is on the order of 10 years or more, so even if it does make it (again, unlikely), it would be at least 10 years before this becomes available to humans. And there's a lot that can go wrong along the way. The biggest problem is that mice are not humans, and as far as animal models go, they're not even a good one. Regarding that 15%, without some error bars (which can be quite large) it will be hard to say how "promising" this actually is.

pcthrowaway 5y ago
Now that we have precedent to fast-track vaccines based on impact of the thing they treat, maybe we can apply this to aging which kills more people per year than pre-vaccine COVID did.
- codeddesign 5y ago
  Haha.. Why test when we can fast-track and test on live people! Great analogy and made me laugh ;)
  - LZ_Khan 5y ago
    Isn't that what we did with Covid vaccines?
    - deleted 5y ago
      [deleted]
    - cinntaile 5y ago
      No, they still went through the different clinical phases that drugs or vaccines go through.
  - simonh 5y ago
    Fast-tracking still involves testing. In the case of the coronavirus vaccine trials, most of them anyway, they went through all the same trials stages any other vaccine would go through. It just happened at a much accelerated tempo, with weeks between trials stages instead of many months or years. Volunteers, trials teams and vaccine stocks for the next stage were already recruited and commissioned before the completion of previous stages anticipating a green light to avoid any delays. There was still time to pull the plug at any stage though, if adverse results had been detected, as did actually happen to several candidate vaccines. The results have been an astounding success, with vaccines that are about as safe and effective as those from previous development processes. So it is possible to safely fast track these projects with enough urgency and investment.
    - InitialLastName 5y ago
      As you say, urgency and investment are key, and neither necessarily applies (or is worth applying) to the general case of medical research (in the absence of a once-in-a-century global urgent surge in demand for a particular slice of medical research). More specifically, it seems like much of this fast-tracking is due to: a) the manufacturers being incentivized to dedicate resources to branch prediction, essentially making the failure path more expensive. and b) the regulator expediting the bureaucracy for a specific set of approvals (essentially jumping the line). Presumably there are other applications that were delayed to support the expedited applications, and I'll bet the expediting process hurt overall bureaucratic efficiency. For A, I'd assume that the option was already priced in by the pharma co's and is (in the non-urgent case) not particularly cost-effective. For B, I'm all for making bureaucratic systems operate more efficiently and responsively, but I'm not convinced that most circumstances are urgent enough to sacrifice throughput to the latency gods.
meitros 5y ago
One thing I never understood is that if results in mice so often don’t carry over to humans, what about the opposite - treatments that might work for people but are discarded because they don’t work well with mice.
- tsol 5y ago
  There are a lot of problems with medical testing, and much of it stems from simple ethics. It would be more effective to test on humans directly and who knows what amazing treatments we might find that don't work in rats. And yet.. that's hopelessly unethical. It reminds me of a scene from House MD; >People should not be testing drugs because they are desperate. But, people won't test drugs unless they are desperate. We need drugs to save children and puppies ergo we need desperate people ergo welfare kills sick children. Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge
  - after_care 5y ago
    > Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge It’s clear to me that modeling the human body would be complicated, but I don’t have any idea about the order of magnitude. Can someone chime in?
    - rmbyrro 5y ago
      I guess the most difficult part is modeling all possible interactions related to an infinity of chemicals, DNA variations, environment influences, past medical issues, etc, etc. I bet this would require computational power equivalent to whatever is "processing" the govern of real-world interactions in our bodies.
    - tsimionescu 5y ago
      Well, to model organic interactions you basically need a molecule-level model of the body or even deeper - especially for extremely complex molecules like proteins (which can famously "fold" in extremely hard to predict ways). So, to very accurately model the human body, you need a model that has as many parameters as there are molecules in a human body, give or take a few orders of magnitude. I have no idea to what extent you could get away with more high-level models - i would expect they could work well for some kinds of problems, but not for very systemic interactions, like hormonal or aging-related issues, that affect each cell in the human body to some extent.
deleted 5y ago
[deleted]
JamesBarney 5y ago
> The biggest problem is that mice are not humans, and as far as animal models go, they're not even a good one. A model != an animal. A model is an animal + process for giving the animal a disease. Mice can be a very good model. As a model for obesity drugs that work through appetite reduction most mouse models are great. For Alzheimer's all models are terrible (amyloid beta injection, genetic over expression of tau, etc). "Mice models are bad" sounds profound but doesn't really say anything. Far more informative to say "mouse models of senolytics are bad, and have poor translation to human trials." But we don't know this because we haven't really tried senolytics in humans, so we have no idea if mice are a good or bad model of human senolytics. I'm idealistic because "mouse gets old and blood vessels don't work as well" is probably pretty similar to "person gets old and blood vessels don't work as well". As opposed to ALS, Alzheimer's, and Parkinson's which mice don't get so we just inject them with stuff we find in the blood and brain of the afflicted.
staticassertion 5y ago
> Results in mice will probably not track to humans, In this case I don't know if that's true. Total layman, but this sounds like autophagy triggered through an immune response. Autophagy is already promising fro human life extension. This feels like an approach that could be generalizable, even if perhaps the specific antibody might not apply.
- chasil 5y ago
  There have been a few past studies on senescent cells with quercetin, both alone and combined with other "senolytics" that have been encouraging. A vaccine would be ideal, but senolytic supplements are likely closer. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(19)30641-3/fulltext https://www.thelancet.com/journals/ebiom/article/PIIS2352-39...
Jansen312 5y ago
They could go along the route of mRNA vaccines. Experimental granted for "emergency use". The rich and powerful will do that. So I doubt it needs 10 years. If they do this altruistically for the masses, yeah 10 is a good number. Not so for the rich and powerful that wish to live immortally.

pcthrowaway 5y ago

Now that we have precedent to fast-track vaccines based on impact of the thing they treat, maybe we can apply this to aging which kills more people per year than pre-vaccine COVID did.

codeddesign 5y ago
Haha.. Why test when we can fast-track and test on live people! Great analogy and made me laugh ;)
- LZ_Khan 5y ago
  Isn't that what we did with Covid vaccines?
  - deleted 5y ago
    [deleted]
  - cinntaile 5y ago
    No, they still went through the different clinical phases that drugs or vaccines go through.
- simonh 5y ago
  Fast-tracking still involves testing. In the case of the coronavirus vaccine trials, most of them anyway, they went through all the same trials stages any other vaccine would go through. It just happened at a much accelerated tempo, with weeks between trials stages instead of many months or years. Volunteers, trials teams and vaccine stocks for the next stage were already recruited and commissioned before the completion of previous stages anticipating a green light to avoid any delays. There was still time to pull the plug at any stage though, if adverse results had been detected, as did actually happen to several candidate vaccines. The results have been an astounding success, with vaccines that are about as safe and effective as those from previous development processes. So it is possible to safely fast track these projects with enough urgency and investment.
  - InitialLastName 5y ago
    As you say, urgency and investment are key, and neither necessarily applies (or is worth applying) to the general case of medical research (in the absence of a once-in-a-century global urgent surge in demand for a particular slice of medical research). More specifically, it seems like much of this fast-tracking is due to: a) the manufacturers being incentivized to dedicate resources to branch prediction, essentially making the failure path more expensive. and b) the regulator expediting the bureaucracy for a specific set of approvals (essentially jumping the line). Presumably there are other applications that were delayed to support the expedited applications, and I'll bet the expediting process hurt overall bureaucratic efficiency. For A, I'd assume that the option was already priced in by the pharma co's and is (in the non-urgent case) not particularly cost-effective. For B, I'm all for making bureaucratic systems operate more efficiently and responsively, but I'm not convinced that most circumstances are urgent enough to sacrifice throughput to the latency gods.

meitros 5y ago

One thing I never understood is that if results in mice so often don’t carry over to humans, what about the opposite - treatments that might work for people but are discarded because they don’t work well with mice.

tsol 5y ago
There are a lot of problems with medical testing, and much of it stems from simple ethics. It would be more effective to test on humans directly and who knows what amazing treatments we might find that don't work in rats. And yet.. that's hopelessly unethical. It reminds me of a scene from House MD; >People should not be testing drugs because they are desperate. But, people won't test drugs unless they are desperate. We need drugs to save children and puppies ergo we need desperate people ergo welfare kills sick children. Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge
- after_care 5y ago
  > Maybe in the future AI will solve this problem, if we can learn to accurately model the human body. But given it's insane complexity that's certainly going to be a big challenge It’s clear to me that modeling the human body would be complicated, but I don’t have any idea about the order of magnitude. Can someone chime in?
  - rmbyrro 5y ago
    I guess the most difficult part is modeling all possible interactions related to an infinity of chemicals, DNA variations, environment influences, past medical issues, etc, etc. I bet this would require computational power equivalent to whatever is "processing" the govern of real-world interactions in our bodies.
  - tsimionescu 5y ago
    Well, to model organic interactions you basically need a molecule-level model of the body or even deeper - especially for extremely complex molecules like proteins (which can famously "fold" in extremely hard to predict ways). So, to very accurately model the human body, you need a model that has as many parameters as there are molecules in a human body, give or take a few orders of magnitude. I have no idea to what extent you could get away with more high-level models - i would expect they could work well for some kinds of problems, but not for very systemic interactions, like hormonal or aging-related issues, that affect each cell in the human body to some extent.

deleted 5y ago

[deleted]

JamesBarney 5y ago

> The biggest problem is that mice are not humans, and as far as animal models go, they're not even a good one. A model != an animal. A model is an animal + process for giving the animal a disease. Mice can be a very good model. As a model for obesity drugs that work through appetite reduction most mouse models are great. For Alzheimer's all models are terrible (amyloid beta injection, genetic over expression of tau, etc). "Mice models are bad" sounds profound but doesn't really say anything. Far more informative to say "mouse models of senolytics are bad, and have poor translation to human trials." But we don't know this because we haven't really tried senolytics in humans, so we have no idea if mice are a good or bad model of human senolytics. I'm idealistic because "mouse gets old and blood vessels don't work as well" is probably pretty similar to "person gets old and blood vessels don't work as well". As opposed to ALS, Alzheimer's, and Parkinson's which mice don't get so we just inject them with stuff we find in the blood and brain of the afflicted.

staticassertion 5y ago

> Results in mice will probably not track to humans, In this case I don't know if that's true. Total layman, but this sounds like autophagy triggered through an immune response. Autophagy is already promising fro human life extension. This feels like an approach that could be generalizable, even if perhaps the specific antibody might not apply.

chasil 5y ago
There have been a few past studies on senescent cells with quercetin, both alone and combined with other "senolytics" that have been encouraging. A vaccine would be ideal, but senolytic supplements are likely closer. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(19)30641-3/fulltext https://www.thelancet.com/journals/ebiom/article/PIIS2352-39...

Jansen312 5y ago

They could go along the route of mRNA vaccines. Experimental granted for "emergency use". The rich and powerful will do that. So I doubt it needs 10 years. If they do this altruistically for the masses, yeah 10 is a good number. Not so for the rich and powerful that wish to live immortally.