I don’t think “Sleep evolved for temporal niches” really explains why sleep is so universal. It that would be all that’s going on I would expect more species that need very little sleep then we are actually observing. The explanation also does relatively poorly at explaining why children would need more sleep than adults.
It might be something more complex like: (1) Animals that aren’t careful tend to take a lot of risks that result in them dying. (2) There’s a process that builds up stress that’s about taking less risks. (3) Sleep exists to process that build-up stress and resolve it.
With that theory you can explain why children for whom taking risk is a bigger deal sleep more than adults. You also can explain how those people with genetic mutations that result in them taking less sleep like Elon Musk take a lot of risks. It explains why the fish that live in the cave where there are no predators or anything risky need less sleep.
Third, any gene therapy for sleep need would have to deliver its payload to the brain.
Why? Orexin-A is perfectly capable of crossing the blood-brain barrier. If you create a gene therapy to produce more of it, it doesn’t need to be produced in the brain.
Other therapeutics like peptides or RNA are harder in every way. They’re expensive to test, expensive to make, and we have less experience trialing them. The body destroys them quickly and you need clever techniques to deliver them to your target.
Why do you believe that? For Orexin-A? You can buy it these days from a neurotropic store if you want as a nasal spray.
The point about children is a good one, I have to think on it more. But it seems consistent with children needing more calories to grow (and they are too young to gather their own calories), so they rest more.
It might be something more complex like: (1) Animals that aren’t careful tend to take a lot of risks that result in them dying. (2) There’s a process that builds up stress that’s about taking less risks. (3) Sleep exists to process that build-up stress and resolve it.
By this do you mean: “when stress builds up, animals take more risks. Risk-taking animals die. Sleep relieves stress, thus enabling less risky behavior?”
It’s a reasonable hypothesis, and I’m open to it happening to some degree. But I think all the arguments against “neurons need rest” apply here just as well. Aren’t there brain regions more or less exposed to stress? Don’t some neurons experience constant (metabolic) stress simply by being active all the time? Are animals with more stress (prey) sleeping more? Do more stressed people adapt by sleeping more?
Why? Orexin-A is perfectly capable of crossing the blood-brain barrier. If you create a gene therapy to produce more of it, it doesn’t need to be produced in the brain.
I should have provided more context, the proposals of Minjune Song and Issak Freeman center on short sleep mutations found in the literature. These are typically mutations of receptors found on neurons in the brain.
Overproducing orexin-A is fine, but a gene therapy for a hormone that can cross the BBB is overkill when you can supply it exogenously right?
By the way, Orexin-A supplementation is the subject of the proposal I mentioned at the end. Should come out today.
Why do you believe that? For Orexin-A? You can buy it these days from a neurotropic store if you want as a nasal spray.
I think you’re mostly asking about production costs right? Yes, you can buy orexin peptides and custom RNA, but the cost-per-unit-effect is orders of magnitude higher than small molecules. It’s hard to beat the ~$100/kg that you can get with generic drug manufacturing.
I’m not just saying “when stress builds up that leads to problem”. The question is why we feel stress in the first place. The question is “What is stress good for?” My idea would be that stress might come out of a process which has the function of inhibiting risk taking.
From a neuroscience perspective I don’t think that “stress is about neurons being used” is a thesis with strong evidence. Two decades ago there was the ridiculous willower is about glucose thesis but that’s wrong. Energy use by the brain does not differ much is “stressful” activities.
I believe that stress is something else. It might be something that exists for the purpose of inhibiting risk taking behavior.
People with so much stress that they have burnout do need more sleep. Otherwise, things are complex. Stress is a pretty broad word and the underlying mechanisms are likely complex. Also my thesis would be that sleep is about releasing stress and there might be situations where the system of a stressed person doesn’t consider it a good idea to release the stress if the stress serves an important purpose by inhibiting behavior.
ChatGPT suggests that children in hunter gather tribes usually get their own food between the ages of 5 and 10. Teenager (14+) still have increased sleep needs compared to adults.
Insulin productions works fine without a commercial need for a insulin analog. Orexin has the advantage that you don’t need to inject it and can use a nasal spray.
Oh I see. So the hypothesis is “In a healthy animal, stress is a highly-informative signal that inhibits risk-taking. Sleep ensures the stress system continues to inhibit risk taking appropriately.”
Makes sense. It’s consistent with sleep deprivation raising the level of cortisol and the brain developing a tolerance to high levels of certain hormones.
I don’t think “Sleep evolved for temporal niches” really explains why sleep is so universal. It that would be all that’s going on I would expect more species that need very little sleep then we are actually observing. The explanation also does relatively poorly at explaining why children would need more sleep than adults.
It might be something more complex like: (1) Animals that aren’t careful tend to take a lot of risks that result in them dying. (2) There’s a process that builds up stress that’s about taking less risks. (3) Sleep exists to process that build-up stress and resolve it.
With that theory you can explain why children for whom taking risk is a bigger deal sleep more than adults. You also can explain how those people with genetic mutations that result in them taking less sleep like Elon Musk take a lot of risks. It explains why the fish that live in the cave where there are no predators or anything risky need less sleep.
Why? Orexin-A is perfectly capable of crossing the blood-brain barrier. If you create a gene therapy to produce more of it, it doesn’t need to be produced in the brain.
Why do you believe that? For Orexin-A? You can buy it these days from a neurotropic store if you want as a nasal spray.
The point about children is a good one, I have to think on it more. But it seems consistent with children needing more calories to grow (and they are too young to gather their own calories), so they rest more.
By this do you mean: “when stress builds up, animals take more risks. Risk-taking animals die. Sleep relieves stress, thus enabling less risky behavior?”
It’s a reasonable hypothesis, and I’m open to it happening to some degree. But I think all the arguments against “neurons need rest” apply here just as well. Aren’t there brain regions more or less exposed to stress? Don’t some neurons experience constant (metabolic) stress simply by being active all the time? Are animals with more stress (prey) sleeping more? Do more stressed people adapt by sleeping more?
I should have provided more context, the proposals of Minjune Song and Issak Freeman center on short sleep mutations found in the literature. These are typically mutations of receptors found on neurons in the brain.
Overproducing orexin-A is fine, but a gene therapy for a hormone that can cross the BBB is overkill when you can supply it exogenously right?
By the way, Orexin-A supplementation is the subject of the proposal I mentioned at the end. Should come out today.
I think you’re mostly asking about production costs right? Yes, you can buy orexin peptides and custom RNA, but the cost-per-unit-effect is orders of magnitude higher than small molecules. It’s hard to beat the ~$100/kg that you can get with generic drug manufacturing.
I’m not just saying “when stress builds up that leads to problem”. The question is why we feel stress in the first place. The question is “What is stress good for?” My idea would be that stress might come out of a process which has the function of inhibiting risk taking.
From a neuroscience perspective I don’t think that “stress is about neurons being used” is a thesis with strong evidence. Two decades ago there was the ridiculous willower is about glucose thesis but that’s wrong. Energy use by the brain does not differ much is “stressful” activities.
I believe that stress is something else. It might be something that exists for the purpose of inhibiting risk taking behavior.
People with so much stress that they have burnout do need more sleep. Otherwise, things are complex. Stress is a pretty broad word and the underlying mechanisms are likely complex. Also my thesis would be that sleep is about releasing stress and there might be situations where the system of a stressed person doesn’t consider it a good idea to release the stress if the stress serves an important purpose by inhibiting behavior.
ChatGPT suggests that children in hunter gather tribes usually get their own food between the ages of 5 and 10. Teenager (14+) still have increased sleep needs compared to adults.
Insulin productions works fine without a commercial need for a insulin analog. Orexin has the advantage that you don’t need to inject it and can use a nasal spray.
Oh I see. So the hypothesis is “In a healthy animal, stress is a highly-informative signal that inhibits risk-taking. Sleep ensures the stress system continues to inhibit risk taking appropriately.”
Makes sense. It’s consistent with sleep deprivation raising the level of cortisol and the brain developing a tolerance to high levels of certain hormones.
Yes, that’s a rough stretch of the idea. Of course, the real details are likely complicated.
It’s worth noting that Orexin does stimulate the hypothalamic-pituitary-adrenal (HPA) axis, which controls cortisol release.