It seems counterintutive that there would be one single thing called “aging” that would happen everywhere in the body at once; have a single cause or even a small set of causes; be measurable by a single “biological age” number; and be slowed, arrested, or reversed by a single intervention… especially an intervention that didn’t have a million huge side effects. In fact, it seems counterintutive that that would even be approximately true. Biology sucks because everything interacts in ways that aren’t required to have any pattern, and are still inconvenient even when they do have patterns.
How do you even do a meaningful experiment? For example, isn’t NAD+ right smack in the middle of the whole cell energy cycle? So if you do something to NAD+, aren’t you likely to have a huge number of really diverse effects that may or may not be related to aging? If you do that and your endpoint is just life span, how do you tease out useful knowledge? Maybe the sirtuins would have extended life span, but for the unrelated toxic effects of all that NAD+. Or maybe the sirtuins are totally irrelevant to what’s actually going on.
The same sort of thing applies to any wholesale messing with histones and gene expression, via sirtuins or however else. You’re changing everything at once when you do that.
Reprogramming too: you mentioned different kinds of cells responding differently. It seems really un-biological to expect that difference to be limited to how fast the cells “come around”, or the effects to be simply understandable by measuring any manageable number of things or building any manageable mental model.
And there are so many other interactions and complications even outside of the results of experiments. OK, senescent cells and inflammation are needed for wound healing… but I’m pretty sure I don’t heal even as fast at over 60 as I did at say 20, even with lots more senescent cells available and more background inflammation. So something else must be going on.
And then there are the side effects, even if something “works”. For example, isn’t having extra/better telomeres a big convenience if you want to grow up to be a tumor? Especially convenient if you’re part of a human and may have decades to accumulate other tricks, as opposed to part of a mouse and lucky to have a year. How do you measure the total effect of something like that in any way other than full-on long-term observed lifespan and healthspan in actual humans?
I’m pretty certain that even if we figure out how to halt or reverse “aging” as in “the (set of) root cause(s) of the progressive syndrome of morbidities and heighten d disease risk universal among 80+ year old people today”, that there would be other forms of long-term accumulating damage to understand and reverse on longer time scales than a single century.
Some examples of long-term accumulating damage that we’ll eventually need to address, but not before people are reliably living to 100+: lead ion accumulation over a lifetime, ditto a bunch of other long-lived poisons, scar tissue accumulation, accumulation of various “dusts” (ex: asbestos) in the lungs, etc.
I think we’re currently, as a civilization, hunting for whatever lifespan/heathspan low-hanging fruit might exist, and will eventually shift to more systematic approaches as our civilization further understands aging and learns to do nanotech.
In the mean time, I’m basically keeping my eyes open for preventable permanent damage sources to avoid, to make my personal time limit less urgent. I take dust inhalation very seriously, ditto trace heavy metal exposure, ditto sunburn.
But does it work at all?
It seems counterintutive that there would be one single thing called “aging” that would happen everywhere in the body at once; have a single cause or even a small set of causes; be measurable by a single “biological age” number; and be slowed, arrested, or reversed by a single intervention… especially an intervention that didn’t have a million huge side effects. In fact, it seems counterintutive that that would even be approximately true. Biology sucks because everything interacts in ways that aren’t required to have any pattern, and are still inconvenient even when they do have patterns.
How do you even do a meaningful experiment? For example, isn’t NAD+ right smack in the middle of the whole cell energy cycle? So if you do something to NAD+, aren’t you likely to have a huge number of really diverse effects that may or may not be related to aging? If you do that and your endpoint is just life span, how do you tease out useful knowledge? Maybe the sirtuins would have extended life span, but for the unrelated toxic effects of all that NAD+. Or maybe the sirtuins are totally irrelevant to what’s actually going on.
The same sort of thing applies to any wholesale messing with histones and gene expression, via sirtuins or however else. You’re changing everything at once when you do that.
Reprogramming too: you mentioned different kinds of cells responding differently. It seems really un-biological to expect that difference to be limited to how fast the cells “come around”, or the effects to be simply understandable by measuring any manageable number of things or building any manageable mental model.
And there are so many other interactions and complications even outside of the results of experiments. OK, senescent cells and inflammation are needed for wound healing… but I’m pretty sure I don’t heal even as fast at over 60 as I did at say 20, even with lots more senescent cells available and more background inflammation. So something else must be going on.
And then there are the side effects, even if something “works”. For example, isn’t having extra/better telomeres a big convenience if you want to grow up to be a tumor? Especially convenient if you’re part of a human and may have decades to accumulate other tricks, as opposed to part of a mouse and lucky to have a year. How do you measure the total effect of something like that in any way other than full-on long-term observed lifespan and healthspan in actual humans?
And and and...
I’m pretty certain that even if we figure out how to halt or reverse “aging” as in “the (set of) root cause(s) of the progressive syndrome of morbidities and heighten d disease risk universal among 80+ year old people today”, that there would be other forms of long-term accumulating damage to understand and reverse on longer time scales than a single century.
Some examples of long-term accumulating damage that we’ll eventually need to address, but not before people are reliably living to 100+: lead ion accumulation over a lifetime, ditto a bunch of other long-lived poisons, scar tissue accumulation, accumulation of various “dusts” (ex: asbestos) in the lungs, etc.
I think we’re currently, as a civilization, hunting for whatever lifespan/heathspan low-hanging fruit might exist, and will eventually shift to more systematic approaches as our civilization further understands aging and learns to do nanotech.
In the mean time, I’m basically keeping my eyes open for preventable permanent damage sources to avoid, to make my personal time limit less urgent. I take dust inhalation very seriously, ditto trace heavy metal exposure, ditto sunburn.