I wonder if perhaps something more environmental might also be playing a part. The protein toxins that are associated with Alzheimer’s seem to build over time and the effectiveness some of the processes that work to clean them up may be negatively impacted they its presence. Seems the the sleep cycle (non-REM) results in a reverse flow type flushing of the brain that help clear this out. But the build up itself seem related to not getting that sleep needed.
So what about internal and external to the cells themselves? Could some elements or combination of things build up that we’re just not looking at yet—have not see it as connected to any of the processes?
I remember that first paper which found some sort of flush-out mechanism for the brain opening up during deep sleep. Do you have a link? I’ve been meaning to dig into that a bit more. I remember when I first saw it I thought it would be huge for understanding Alzheimers, but that was a while ago before I started seriously reading up on aging.
Anyway, environmental factors...
There’s a qualitative general pattern that various kinds of physiological stress—exposure to radiation or harsh chemicals (including smoking), chronic infection, malnutrition, sleep deprivation, etc—tend to accelerate aging. These are results which I generally don’t put too much faith in, at least individually—they’re too flashy, so there’s likely publication bias. That said, there is a plausible mechanism by which general physiological insults would accelerate aging. I’ll save discussion of that for a later post, but David Sinclair published a (general-audience) book earlier this year which discusses it quite a bit.
One important thing to note, more related to the OP: whatever the root causes of aging are, i.e. the things which are out-of-equilibrium on long timescales, those do need to be internal to the organism. We would have noticed centuries ago if changing the environment could forestall aging long-term. That does not mean these factors need to be inside particular cells; for instance, extracellular aggregation of certain long-lived proteins is one plausible root cause (e.g. elastin deposits as a cause of wrinkles). It is very likely that we are still missing connections in the causal graph, so there could easily be things building up that we’re not paying attention to yet. That said, there are relatively few things in the body which turn over on decade-plus timescales, so that severely limits the list of possible root causes.
Here is one link: https://www.sciencedaily.com/releases/2019/10/191031174650.htm . I was not able to find the one I was actually reading earlier (and apparently my poor sleep last night was not sufficient and I cannot remember how I found it....) but the link here seems to be referencing the study I was reading about.
BTW, when I mentioned “external” I was not thinking external to the organism (e.g., me) but rather external to the cells (or at least many of them) but within the confines of our body or organ.
Alzheimer’s, and several other age-related diseases, seem to be related to lifestyle, since they’re rare enough in hunter-gatherer tribes that they can’t be detected.
The kinds of age-related deaths that are common to all environments are mainly due to frailty, susceptibility to infectious diseases, and cancer.
Frailty seems a questionable cause in this context. Am in interpreting incorrectly perhaps?
I would think frailty while young might be a symptom of something that leads to death but how do we go from “sturdy” and so healthy and living well (in a functional sense) to old and frail and more likely to die?
The other two, seem more like lottery type cases, yes we all have a probability of contracting some infection or virus that our immune systems just cannot deal with so we die. We have a probability of cancer destroying critical systems. But that doesn’t quite explain the whole aging story to me—why the slow path to what we see physically rather than a sudden break? Or is this inference about how we should observe things missing something you perhaps have bundled into the three causes you mention above I perhaps I should understand why (if I were more knowledgeable on this area)?
I wasn’t trying to describe the root causes of aging. I was trying to distinguish between diseases that are avoidable via lifestyle changes, and age-related diseases that are sufficiently determined by our genes that we’ll need major new technology to avoid them. The latter include things that impair our immune system and repair mechanisms.
My best guess is that the root causes of aging involve some clock-like processes that have been actively selected for different metabolism at different ages. See Josh Mitteldorf’s writings if you want more on that topic.
I wonder if perhaps something more environmental might also be playing a part. The protein toxins that are associated with Alzheimer’s seem to build over time and the effectiveness some of the processes that work to clean them up may be negatively impacted they its presence. Seems the the sleep cycle (non-REM) results in a reverse flow type flushing of the brain that help clear this out. But the build up itself seem related to not getting that sleep needed.
So what about internal and external to the cells themselves? Could some elements or combination of things build up that we’re just not looking at yet—have not see it as connected to any of the processes?
I remember that first paper which found some sort of flush-out mechanism for the brain opening up during deep sleep. Do you have a link? I’ve been meaning to dig into that a bit more. I remember when I first saw it I thought it would be huge for understanding Alzheimers, but that was a while ago before I started seriously reading up on aging.
Anyway, environmental factors...
There’s a qualitative general pattern that various kinds of physiological stress—exposure to radiation or harsh chemicals (including smoking), chronic infection, malnutrition, sleep deprivation, etc—tend to accelerate aging. These are results which I generally don’t put too much faith in, at least individually—they’re too flashy, so there’s likely publication bias. That said, there is a plausible mechanism by which general physiological insults would accelerate aging. I’ll save discussion of that for a later post, but David Sinclair published a (general-audience) book earlier this year which discusses it quite a bit.
One important thing to note, more related to the OP: whatever the root causes of aging are, i.e. the things which are out-of-equilibrium on long timescales, those do need to be internal to the organism. We would have noticed centuries ago if changing the environment could forestall aging long-term. That does not mean these factors need to be inside particular cells; for instance, extracellular aggregation of certain long-lived proteins is one plausible root cause (e.g. elastin deposits as a cause of wrinkles). It is very likely that we are still missing connections in the causal graph, so there could easily be things building up that we’re not paying attention to yet. That said, there are relatively few things in the body which turn over on decade-plus timescales, so that severely limits the list of possible root causes.
Here is one link: https://www.sciencedaily.com/releases/2019/10/191031174650.htm . I was not able to find the one I was actually reading earlier (and apparently my poor sleep last night was not sufficient and I cannot remember how I found it....) but the link here seems to be referencing the study I was reading about.
BTW, when I mentioned “external” I was not thinking external to the organism (e.g., me) but rather external to the cells (or at least many of them) but within the confines of our body or organ.
[Just found it with a different seach. https://www.sciencenews.org/article/sleep-may-trigger-rhythmic-power-washing-brain ]
Aha, that study linked to the one I was thinking of: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880190/
Thanks!
Alzheimer’s, and several other age-related diseases, seem to be related to lifestyle, since they’re rare enough in hunter-gatherer tribes that they can’t be detected.
The kinds of age-related deaths that are common to all environments are mainly due to frailty, susceptibility to infectious diseases, and cancer.
Do you have a reference for that Alzheimer’s thing? I’d be interested to read more.
My main source is Food and Western Disease: Health and Nutrition from an Evolutionary Perspective, by Staffan Lindeberg .
Frailty seems a questionable cause in this context. Am in interpreting incorrectly perhaps?
I would think frailty while young might be a symptom of something that leads to death but how do we go from “sturdy” and so healthy and living well (in a functional sense) to old and frail and more likely to die?
The other two, seem more like lottery type cases, yes we all have a probability of contracting some infection or virus that our immune systems just cannot deal with so we die. We have a probability of cancer destroying critical systems. But that doesn’t quite explain the whole aging story to me—why the slow path to what we see physically rather than a sudden break? Or is this inference about how we should observe things missing something you perhaps have bundled into the three causes you mention above I perhaps I should understand why (if I were more knowledgeable on this area)?
I wasn’t trying to describe the root causes of aging. I was trying to distinguish between diseases that are avoidable via lifestyle changes, and age-related diseases that are sufficiently determined by our genes that we’ll need major new technology to avoid them. The latter include things that impair our immune system and repair mechanisms.
My best guess is that the root causes of aging involve some clock-like processes that have been actively selected for different metabolism at different ages. See Josh Mitteldorf’s writings if you want more on that topic.