Well, there is the old argument, partially semantic, whether aging is a disease (or collection of diseases) or a natural process that’s the result of how the body is designed (designed in the sense of construction by evolution). You seem to favor the “aging is a disease” model. I favor the “aging is the result of evolutionary design”.
We all agree that bodies fail and die as a result of aging. They can also fail and die as a result of disease - I think(?) we agree on that too. But a more subtle point is that in my understanding bodies must age and die without disease being the driver of that failure and death - this is where I believe we differ. Correct me if I’m wrong in understanding your position.
Why do I think aging and death are not result of disease, but a direct consequence of design can be incapsulated in the concept of how telomeres work. Telomeres are a cap on the amount of time a cell can last controlled by number of divisions. When a telomere reaches critical length as a result of a number of divisions, the cell stops, senesces and dies. It does not need a disease to die. Disease does not drive the demise of the cell, the cell demise is designed into the very construction of the cell - this is aging (and eventual death). In other words, cells do not need disease to kill them, they die by design.
This can be extrapolated to the whole organism. As the body ages, its resilience drops, the ability to repair drops, recovery to homeostasis drops. These are natural processes which are the result of how the body is designed, not the result of any particular disease. When the body reaches the limits of its design, the stem cells have been depleted, there is no more recovery, failure occurs. The acute event can be whatever the organ or system fails irrecoverably first - heart, brain, kidneys whatnot, whatever system resources cannot bring to homeostasis.
Now, it is true, that while the system ages and resilience drops and the ability to repair drops, the instances of non-communicable (and communicable!) diseases increase, and various vulnerabilities (cardiovascular risk factors, excessive ApoB production, dysregulated glucose metabolism etc.) translate into much increased rates. That is why these diseases increase with age, not because age causes them, but because as a result of age related changes the body can no longer defend against them.
This is where an element of semantic argument enters. If you are sitting in a secure home and outside the home are bandits seeking to harm you, but a family member Mr. Aging systematically dismantles the defenses in the house [by design - that’s what aging is], then eventually bandits will be able to breach the walls and start assaulting you. Now the question becomes - has Mr. Aging [age process] killed you, or did the bandits [disease].
Now consider the Blue Zones. I’d argue these populations have effectively slowed their rate of aging. They still die of the same diseases as everyone else—just later. The whole curve shifts to the right by about a decade.
Again, we might be getting into semantics here, but no, I don’t think blue zone populations have slowed their rate of aging. I think they have simply come closer to the full biological potential of human body design.
So here’s the practical takeaway: if your lifestyle or interventions are expected to delay your biological aging, it stands to reason that the onset of age-related diseases will be delayed as well.
No, I don’t think lifestyle and such interventions are expected to delay biological aging, they are expected to prevent premature succumbing to pathologies due to weaker defenses, weaker defenses brought on by the insults of unhealthy lifestyle and environment.
I think the following thought experiment can clarify our positions. Let us assume two identical individuals “A” and “B” with exactly the same lifestyles. They have the same biological profile and exactly the same rate of aging and the same disease - here we can pick anything we want, let us assume it’s atherosclerosis, which will kill them both at 75. You will say that the atherosclerosis - or AD, or whatnot is a manifestation of the aging process that killed them. I say it is a disease that killed them - atherosclerosis, AD whatnot, prematurely.
If I now put A on an effective lipid lowering therapy starting in youth - say a statin - “A” will live to 85, so a decade longer than “B” who was not put on a statin. “A” lived a decade longer because I stopped the disease process, not because I slowed down A’s aging. I wish to have a “statin” for AD. That too, will not slow the aging, but it will cure the disease and allow A to reach the full biological potential of his design, which is 85 - I have not slowed down the aging. Now, maybe (and that’s a big “maybe”) rapamycin would actually slow aging, and now A would reach 95, but for real results you have to change the original design, in the same way in which two extremely similar animals - both small rodents - the mouse and the naked mole rat have a very different genetic design, so one lives around 3 years at best and the other over 30. You cannot do that with any current lifestyle or drug intervention. Optimal lifestyle on the mouse gets you to 3 years, add rapamycin or longevity drug X, maybe get to as much as 4 years, but only a change of design will get that mouse to 30+.
Here is why our perspectives have practical consequences. If you treat AD as a disease of aging, where you need to slow down the aging to delay the onset of AD, then you are asking for a moonshot - you are asking to slow down the rate of aging, which we have no tools to do at present other than two - count them, TWO - interventions in model animals (CR and possibly rapamycin). That’s it. We have no other way to provably slow biological aging in mammals at present. I think that slowing down aging in humans is a HUGE ask. And ultimately, by your own words, it merely delays AD. Now, my approach is to treat AD as a distinct disease, just as atherosclerosis is - and I want to cure it. I want to eliminate AD, not just delay it. We have done so successfully with atherosclerosis, where by getting to rock bottom ApoB we have essentially stopped the pathology - and not merely delayed it. I want to stop AD.
Therefore framing AD and such diseases as diseases distinct from the aging process (even if prevalence increases with age), allows us to search for a cure without having to hunt for Ponce de Leon type moonshots. I’d love to slow down aging, absolutely, but I would also like to cure diseases in the meantime, I don’t want to wait until we all live to 150, because a lot of people get AD and such at much, much earlier ages. We should work on both, but I expect faster results from treating AD as a disease.
