I think we should start with something smaller. Like rats, or smaller still.
Can you keep a cactus or flower alive forever? What about a bug? Starting small and then eventually being able to help larger animals and humans seem like an obvious choice here, but I’ve never heard about somebody trying to extend the life of snails or simple plants before.
I’ve read enough about nootropics to know that biology is complicated and that you can’t just give X drugs because X correlates with Y and because Y is good.
It’s bad science. And yeah, there’s lots of money in promoting “healthy things” which aren’t actually healthy, and in strongly exaggerating positive effects and not warning about side-effects. In order to get other people to give you money or invest in your ideas, you often have to lie or exaggerate. This is a fundemental problem of society, if not just how things work.
I haven’t done a similar search for lab mice (Mus musculus), but I expect that such a search would turn up similar results.
I think moving on to dogs does make sense, but my uninformed inclination is to agree with OP that I’m not super hopeful about the efficacy of LOY-001. Although also I’d like to point out that this is a treatment for dogs, and so I think it’s good that the FDA is not being extremely strict when safety has been demonstrated and there’s a halfway plausible story of efficacy. Unless this causes a backlash against the FDA doing sensible things I guess.
Well, I see that there’s a lot of research, but it’s all quite minor, like allowing a specific species to live 10% longer by messing with a few genes. This is more or less rounding-errors in the grand quest for human immortality, at least from my birds-eye perspective. If we can’t make a simple insect or plant live forever, then I don’t think we understand death well enough to warrant experimenting with dogs and humans. Ethically, it’s also better to experiment with very simple life-forms, and if we can’t make those live forever, then we have no hope with humans.
To begin with, death is fascinating in that things generally grow bigger and stronger and better, and then just suddenly start to degenerate despite still having all the resources which lead to growth. Logically speaking, death isn’t actually required in any sense, and yet it seems to happen in basically all forms of life ever discovered or created. More interestingly, it also seems to happen for things like countries, companies, products and communities, even as they change for the sake of “improvement”, so if some natural law was to limit the life-span of all things to some level of total internal activity (perhaps entropy?), we could prove immortality to be impossible.
This “activity” law seem to be true, you can probably make things live longer by decreasing the rate of metabolism, but the total amount of actions is the same, you’re just making them happen more slowly. So it’s likely that a lot of drugs can make us live longer, but that there’s a hidden cost (another post suggests that igf-01 could lead to slower recovery of injury, so perhaps the drug just makes one live ‘slower’ rather than ‘longer’). That said, life appear to have a optimal amount of resistance optimal for growth, both too little exercise and too much exercise will cause us to die faster.
Not to downplay the value or difficulty of more tedius and “safe” approaches to science. Immortality is obviously a very difficult topic.
I think using dogs for life extension research makes at least as much sense as raising pigs for food.
More interestingly, it also seems to happen for things like countries, companies, products and communities
I think this is a function of “create a new instance of something” being an easier problem than “fix a broken instance of that thing”. If there are any types of damage that you can’t fix, you will accumulate those types of damage over time. Consider teeth—pretty simple to grow, but once they’re exposed to the world your body can’t repair them, so they’ll degrade over time.
Relatedly, I’m pretty bullish on the “grow a new copy of the things that are breaking down and replace the worn out ones with new ones” approach for those organs where it’s viable to do so. Unfortunately that does not include brains.
That makes sense! If it’s ‘cheaper’, then evolution will choose it. Thinking about it, I also think that we sometimes kill or replace parts of something so that the rest can live. If we have bad habits, then we need to kill said habits before they kill us.
I’ve long thought that adaptability is important to survival, and that inflexibility means death, but it makes sense that we haven’t evolved ways to heal all kind of damage, and that certain noise/damage/waste accumulate until we break.
Depending on what you meant by “we should start with” this comment might not apply.
I would think an interesting comparison to add to the argument’s in the OP (And, I thought it a good call out. Thanks.) might be looking at IGF-1 in naked mole-rats. They seem to have a good track record with respect to aging processes. If they don’t show the implied relation between IGF-1 and their good aging attribute then why expect that in dog, or cats, other pet animals (or farm animals) or humans?
Very late response but that was just saying, from my cursory knowledge, that everyone seems to agree that naked mole-rats do not seem to display the same aging related problems other species do.
Naked mole rats exhibit unique characteristics related to Insulin-like Growth Factor 1 (IGF-1). These animals are known for their exceptionally long lifespans relative to their size and their remarkable resistance to cancer. Studies have shown that differences in the IGF-1 pathway in naked mole rats contribute to these traits.
IGF-1, a hormone similar in molecular structure to insulin, plays a significant role in growth during childhood and continues to have anabolic effects in adults. In most mammals, including humans, IGF-1 is a critical component in the regulation of growth and development, and it has been implicated in the aging process and cancer development.
In naked mole rats, however, there are several unique aspects:
Reduced IGF-1 Signaling: Naked mole rats have lower levels of IGF-1 and reduced IGF-1 signaling compared to other mammals. This reduced signaling is thought to contribute to their slow growth rates and small adult size.
Longevity and Aging: The altered IGF-1 pathway in naked mole rats is believed to be one of the factors contributing to their extended lifespan and healthspan. In many species, reduced IGF-1 signaling is associated with longer lifespans, and this seems to be the case with naked mole rats as well.
Cancer Resistance: Naked mole rats are remarkably resistant to cancer, and this resistance is partly attributed to their unique IGF-1 signaling pathways. Their cells have a heightened sensitivity to contact inhibition, a process where cells stop growing when they come into contact with each other, which is a mechanism that can prevent cancerous growth.
Metabolic Stability: Naked mole rats maintain stable metabolic rates and body temperatures, despite living in fluctuating underground environments. This stability might be influenced by their unique hormonal regulation, including IGF-1.
Overall, the unique aspects of IGF-1 in naked mole rats are a significant area of research, especially in the context of aging, cancer biology, and understanding the mechanisms of longevity.
I think we should start with something smaller. Like rats, or smaller still.
Can you keep a cactus or flower alive forever? What about a bug? Starting small and then eventually being able to help larger animals and humans seem like an obvious choice here, but I’ve never heard about somebody trying to extend the life of snails or simple plants before.
I’ve read enough about nootropics to know that biology is complicated and that you can’t just give X drugs because X correlates with Y and because Y is good.
It’s bad science. And yeah, there’s lots of money in promoting “healthy things” which aren’t actually healthy, and in strongly exaggerating positive effects and not warning about side-effects. In order to get other people to give you money or invest in your ideas, you often have to lie or exaggerate. This is a fundemental problem of society, if not just how things work.
I think there is extensive longevity research on smaller animals. For example, for fruit flies a cursory search turns up
Protocols to Study Aging in Drosophila
Ageing in Drosophila: The role of the insulin/Igf and TOR signalling network
On the developmental theory of ageing. I. Starvation resistance and longevity in Drosophila melanogaster in relation to pre-adult breeding conditions
Analysing variation in Drosophila aging across independent experimental studies: a meta-analysis of survival data
Cultural artifacts: a comparison of senescence in natural, laboratory-adapted and artificially selected lines of Drosophila melanogaster
Sex-specific effects of interventions that extend fly life span
Testing an ‘aging gene’ in long-lived Drosophila strains: increased longevity depends on sex and genetic background
I haven’t done a similar search for lab mice (Mus musculus), but I expect that such a search would turn up similar results.
I think moving on to dogs does make sense, but my uninformed inclination is to agree with OP that I’m not super hopeful about the efficacy of LOY-001. Although also I’d like to point out that this is a treatment for dogs, and so I think it’s good that the FDA is not being extremely strict when safety has been demonstrated and there’s a halfway plausible story of efficacy. Unless this causes a backlash against the FDA doing sensible things I guess.
Well, I see that there’s a lot of research, but it’s all quite minor, like allowing a specific species to live 10% longer by messing with a few genes. This is more or less rounding-errors in the grand quest for human immortality, at least from my birds-eye perspective. If we can’t make a simple insect or plant live forever, then I don’t think we understand death well enough to warrant experimenting with dogs and humans.
Ethically, it’s also better to experiment with very simple life-forms, and if we can’t make those live forever, then we have no hope with humans.
To begin with, death is fascinating in that things generally grow bigger and stronger and better, and then just suddenly start to degenerate despite still having all the resources which lead to growth. Logically speaking, death isn’t actually required in any sense, and yet it seems to happen in basically all forms of life ever discovered or created. More interestingly, it also seems to happen for things like countries, companies, products and communities, even as they change for the sake of “improvement”, so if some natural law was to limit the life-span of all things to some level of total internal activity (perhaps entropy?), we could prove immortality to be impossible.
This “activity” law seem to be true, you can probably make things live longer by decreasing the rate of metabolism, but the total amount of actions is the same, you’re just making them happen more slowly. So it’s likely that a lot of drugs can make us live longer, but that there’s a hidden cost (another post suggests that igf-01 could lead to slower recovery of injury, so perhaps the drug just makes one live ‘slower’ rather than ‘longer’). That said, life appear to have a optimal amount of resistance optimal for growth, both too little exercise and too much exercise will cause us to die faster.
Not to downplay the value or difficulty of more tedius and “safe” approaches to science. Immortality is obviously a very difficult topic.
I think using dogs for life extension research makes at least as much sense as raising pigs for food.
I think this is a function of “create a new instance of something” being an easier problem than “fix a broken instance of that thing”. If there are any types of damage that you can’t fix, you will accumulate those types of damage over time. Consider teeth—pretty simple to grow, but once they’re exposed to the world your body can’t repair them, so they’ll degrade over time.
Relatedly, I’m pretty bullish on the “grow a new copy of the things that are breaking down and replace the worn out ones with new ones” approach for those organs where it’s viable to do so. Unfortunately that does not include brains.
That makes sense! If it’s ‘cheaper’, then evolution will choose it. Thinking about it, I also think that we sometimes kill or replace parts of something so that the rest can live. If we have bad habits, then we need to kill said habits before they kill us.
I’ve long thought that adaptability is important to survival, and that inflexibility means death, but it makes sense that we haven’t evolved ways to heal all kind of damage, and that certain noise/damage/waste accumulate until we break.
Depending on what you meant by “we should start with” this comment might not apply.
I would think an interesting comparison to add to the argument’s in the OP (And, I thought it a good call out. Thanks.) might be looking at IGF-1 in naked mole-rats. They seem to have a good track record with respect to aging processes. If they don’t show the implied relation between IGF-1 and their good aging attribute then why expect that in dog, or cats, other pet animals (or farm animals) or humans?
What is “a good track record with respect to aging processes” referring to?
Very late response but that was just saying, from my cursory knowledge, that everyone seems to agree that naked mole-rats do not seem to display the same aging related problems other species do.
ChatGPT’s opinion on IGF-1 in naked mole rats: