6 ms·

This - it's more like an end-stage failure mode of a self-regulating, dynamic system which has drifted into dysfunction. A case of "lots of things have to work

This - it's more like an end-stage failure mode of a self-regulating, dynamic system which has drifted into dysfunction. A case of "lots of things have to work perfectly, or near enough, or a brain drifts into this state". This seems to be very much the case with cancers, essentially unless everything regulates properly, the system would on its own devolve into cancer. Like a gyroscope which will only spin if balanced, only this gyroscope has 10^LARGE moving parts. And when you consider the ageing process, you're talking about multiple systems operating at 50%, 75%, 85% effectiveness, all of which interact with one another, so it's inevitable that self-regulating mechanisms start to enter failure cascade. In terms of interventions, a lot of the time it seems like the best fix is to look at which of the critical systems is most deteriorated, and try and bring that one up. So, for example, diet and exercise can restore a degraded circulatory system by a meaningful amount, but you can be an Ironman triathlete and still develop Alzheimers in your 60s. If we can find reliable ways to do the same for sleep, that will be worthwhile, and likely there are other systems where we might do the same - immune, liver, kidneys and so on.

HPsquared 2y ago
It sounds like corrosion in metals. There are many different damage mechanisms and protective effects, but at the end of the day you see weakened, oxidised metal.
- Earw0rm 2y ago
  Yes, except that metal isn't a dynamic, self-regulating structure. The body is in a constant state of actively fighting against its own decay.
  - HPsquared 2y ago
    Passivation is a similar kind of dynamic balance. Formation of a protective oxide layer. That's how stainless steel, aluminium don't corrode despite being pretty reactive. See also galvanized steel, which is also pretty dynamic with all the electrochemistry, transfer processes and kinetics going on.
pedalpete 2y ago
The sleep bit is what we are working on. We increase slow-wave delta power, increasing the effectiveness of the glymphatic system to flush metabolic waste from the brain. There is more than a decade of research into this process, the studies I pointed at earlier are focused on older adults, which see a larger improvement than a younger population, but lots of studies in university aged subjects due to the nature of research. We have links to more of the research papers on our website https://affectablesleep.com/research https://affectablesleep.com/research
- Earw0rm 2y ago
  So I absolutely think you're on the right track, but also you've got a product to sell. Certainly piqued my interest at least, depending on price point, how long it takes to demonstrate effectiveness and so on.
  - pedalpete 2y ago
    If we're talking about effectiveness in AD, there are LOTS more studies to go, so I don't expect to see a result there for at least 5 years. However, effectiveness is subjectively felt on day one (depending on your current sleep habits, it's more effective in people who are somewhat sleep deprived). We link to a bunch of the existing research on our website, and more than just "sleep time" we can track effectiveness to biomarkers such as HRV.
dsign 2y ago
This is spot-on. A corollary is that the best way to fight these diseases is by doing "maintenance" early on. But we currently don't have good enough models of all those multiple systems, and a functional, "good" state may vary significantly from individual to individual. Yet, those computational models could, in due time, save lives. Be as it may, I don't believe we can create those models manually, one by one. It's just too complicated and costly, and as this article shows, prone to turf politics. The good news is that we are having great advances in molecular simulation, and there are gargantuan investments coming to develop the world's computational capabilities. Furthermore, even the current crop of AI tools is good enough to locate and make information accessible to non-experts. So, if you are looking for a hobby in front of a computer, consider given these computational problems some attention.
- Earw0rm 2y ago
  Yep, I neglected to consider that the system isn't just self-regulating but also self-calibrating. Even if we can't _fix_ all those systems, getting reliable predictive/status markers would be a good start. Just being able to scan for ten or twenty blood markers and work out which aspect/s of health someone needs to focus their efforts on improving. It doesn't feel like we're a million miles from being able to do that now. As to the multiple systems - we probably want to add hormonal and short/medium term regulatory systems to that list (being able to activate even a 40yr old's motivational/dopamine response in a 75yr old would be a significant step). And take into account that there are designed-in trade-offs (slower cellular repair in ageing bodies is very possibly an evolutionary adaptation to deal with higher cancer risk in cells with more mutation damage, for example).
  - thereticent 2y ago
    You just described the exact end goal of my overall research program, if we can keep the stroke, AD, and Down syndrome + AD cohorts running. Associating blood biomarkers differentially with individual disease processes and comorbid health factors is the holy grail. Perverse professional norms and plenty of miscreants have made it a much harder road for other dementia researchers, but it's worth keeping on, and there are so many avenues that haven't been pursued.

HPsquared 2y ago

It sounds like corrosion in metals. There are many different damage mechanisms and protective effects, but at the end of the day you see weakened, oxidised metal.

Earw0rm 2y ago
Yes, except that metal isn't a dynamic, self-regulating structure. The body is in a constant state of actively fighting against its own decay.
- HPsquared 2y ago
  Passivation is a similar kind of dynamic balance. Formation of a protective oxide layer. That's how stainless steel, aluminium don't corrode despite being pretty reactive. See also galvanized steel, which is also pretty dynamic with all the electrochemistry, transfer processes and kinetics going on.

pedalpete 2y ago

The sleep bit is what we are working on. We increase slow-wave delta power, increasing the effectiveness of the glymphatic system to flush metabolic waste from the brain. There is more than a decade of research into this process, the studies I pointed at earlier are focused on older adults, which see a larger improvement than a younger population, but lots of studies in university aged subjects due to the nature of research. We have links to more of the research papers on our website https://affectablesleep.com/research https://affectablesleep.com/research

Earw0rm 2y ago
So I absolutely think you're on the right track, but also you've got a product to sell. Certainly piqued my interest at least, depending on price point, how long it takes to demonstrate effectiveness and so on.
- pedalpete 2y ago
  If we're talking about effectiveness in AD, there are LOTS more studies to go, so I don't expect to see a result there for at least 5 years. However, effectiveness is subjectively felt on day one (depending on your current sleep habits, it's more effective in people who are somewhat sleep deprived). We link to a bunch of the existing research on our website, and more than just "sleep time" we can track effectiveness to biomarkers such as HRV.

dsign 2y ago

This is spot-on. A corollary is that the best way to fight these diseases is by doing "maintenance" early on. But we currently don't have good enough models of all those multiple systems, and a functional, "good" state may vary significantly from individual to individual. Yet, those computational models could, in due time, save lives. Be as it may, I don't believe we can create those models manually, one by one. It's just too complicated and costly, and as this article shows, prone to turf politics. The good news is that we are having great advances in molecular simulation, and there are gargantuan investments coming to develop the world's computational capabilities. Furthermore, even the current crop of AI tools is good enough to locate and make information accessible to non-experts. So, if you are looking for a hobby in front of a computer, consider given these computational problems some attention.

Earw0rm 2y ago
Yep, I neglected to consider that the system isn't just self-regulating but also self-calibrating. Even if we can't _fix_ all those systems, getting reliable predictive/status markers would be a good start. Just being able to scan for ten or twenty blood markers and work out which aspect/s of health someone needs to focus their efforts on improving. It doesn't feel like we're a million miles from being able to do that now. As to the multiple systems - we probably want to add hormonal and short/medium term regulatory systems to that list (being able to activate even a 40yr old's motivational/dopamine response in a 75yr old would be a significant step). And take into account that there are designed-in trade-offs (slower cellular repair in ageing bodies is very possibly an evolutionary adaptation to deal with higher cancer risk in cells with more mutation damage, for example).
- thereticent 2y ago
  You just described the exact end goal of my overall research program, if we can keep the stroke, AD, and Down syndrome + AD cohorts running. Associating blood biomarkers differentially with individual disease processes and comorbid health factors is the holy grail. Perverse professional norms and plenty of miscreants have made it a much harder road for other dementia researchers, but it's worth keeping on, and there are so many avenues that haven't been pursued.