#1

The aging field need to clean up its act immediately and stop attributing common diseases to the aging process. I don’t know if it’s because aging experts are uneducated outside their field, but many of the primary diseases causing disability and death with increasing age over normal lifespans have nothing to do with aging but lifestyle or exposure and time. This might be the reason why few take the field seriously, it’s because the aging influencers doesn’t either or feel like massaging the truth.

This is proven by the fact that Type 2 Diabetes can be reversed by losing excess body fat, and that ASCVD process can be stopped with genes leading to loss of function of PCSK9 and a lifetime reduction in LDL-C levels – nothing to do with aging at all. Likewise we have atherosclerotic plaque in young individuals, and hypertension isn’t observed to develop with increasing age in low sodium intake and fit populations.

So groundbreaking research isn’t required for many of the common diseases, we already know many of the causes. Remove the right amount of cases from every graph showing disease prevalence over time and attribute correctly which ones are caused by aging and when, those are important to tackle for longer health and lifespans, the other tools available today can be used for the rest. It’s more effective as well, simple, and doesn’t make longevity experts come off as used car salesmen who don’t know what they’re talking about.

Basically lumping everything into “Age-related disease” is dishonest when we know how many cases are time and exposure related. Or should people use this as a “noble lie”? I don’t think it’s going to work and will just confuse people, at least when it comes to their own health.

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#2

I have to agree. But it’s even more puzzling when diseases which only afflict a minority of the population, such as AD are attributed to aging. With atherosclerosis affecting the majority of (Western) populations, perhaps one might mistakenly conflate it wth aging, but if, say, only a third get AD, it means 2/3 do not, so how is it the result of aging when two thirds of old people don’t experience it. And women getting more AD, does it mean women age more? And different rates of AD in different countries, does it mean different rates of aging in different countries? It makes no sense.

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#3

Well the argument is if we lived long enough we might all get AD. Different organs age at different rates. Just because something else is likely to kill most before AD gets them doesn’t prove AD is not a byproduct of aging. Women live longer than men so… that makes them on average more likely to catch that particular bullet.

Not making any assertion either way regarding the item in contention.

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#4

Sure, but AD is still a disease, and not part of the process of normal aging. You can also be genetically susceptible to any given disease, be it sickle cell anemia, atherosclerosis or Alzheimer’s disease. Same is true in the opposite direction: you might be genetically protected against a disease, atherosclerosis or Alzheimer’s disease, etc. Why? Because these are diseases. Nobody is genetically protected against aging itself (except some crustaceans and the like). If AD were an inevitable result of aging, everyone would get it if they lived long enough and therefore the very oldest, like centenarians ought to have it 100%. But it is a disease and not only do not all centenarians get it despite extreme old age, but some are genetically protected against this disease. Rates of Alzheimer’s Disease increase with age, just like rates of many, many diseases increase with age, but it remains a disease and not part of aging itself - it is a pathology.

Cognitively healthy centenarians are genetically protected against Alzheimer’s disease

#5

We all hear post hoc ergo propter hoc or correlation does not imply causation. The tools of causal inference let us investigate the reasons why.

Does the faucet being opened all the way cause the bathtub to fill or does the passage of time? Do elevated apoB particle count and inflammation cause ASCVD or does the passage of time? You can’t really separate the two in that way.

If aging is just a catch-all for the various insults that degrade the functionality of a body, ASCVD is not caused by aging…ASCVD is aging. Particularly for those aging clocks that aim to correlate rate of aging with rate of decrease in time to death, we can say that smoking one cigarette causes a small acceleration in aging and getting hit by a bus causes a large acceleration in aging. And it stands to reason: getting hit by a bus certainly degrades the function of one’s body!

As is often the case when one tries to think rigorously about a concept, one discovers that the hand-wave definitions that hold up perfectly well for casual conversation fail when the epistemic demands are ratcheted higher. Questions about causality have a way of doing that.

I would posit that time + insults cause aging, which is best characterized as an ensemble measure of changes to organ systems that degrade the function of the body. Until we have stasis chambers, near light speed travel, or hibernation serum, time is effectively exogenous. We all experience one day of time per calendar day. What differs is the insults we subject ourselves to during the course of those calendar days.

Hence it is sensible to treat as causal of aging any insult that is likely to degrade a body’s functionality when stretched out over the period of time one hopes their body’s function will be maintained. This is also why the heart health guidelines that look at ten-year risk (as anything other than a proxy for lifetime risk) are galling: I don’t want a heart attack in the next ten years or in year eleven. Is there “heart aging” separate from “heart disease”? I don’t know how we make that distinction.

What the people on this forum mostly have in common is a belief that they stand to benefit by adopting habits—whether sleep, diet, or drug—that reduce the amount of insult per unit time.

There is a tantalizing question—might there be some kind of universal insult, some equivalent of trying to drive with the emergency brake engaged—that we could modify to achieve what people colloquially refer to as “treating aging directly,” or is it always going to be a matter of what looks like reducing insults that over time damage one or more organ systems.

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#6

Aging is not just an accumulation of damage, otherwise statistics show us that we’d expect some people to have lived for longer than 122 already.

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#7

There is no sense going round the houses on these things. I will not respond further on this topic, but

a) It is entirely possible that different people have different diseases in different orders and that everyone might have AD (for example) if they lived to 300.

b) I think there are diseases which are partially age related and partially caused by other things, T2D, AD, ASCVD, Cancer fall into those categories.

However, we can simply agree to disagree about this. Over time we will find out more about the science and come to a settled conclusion. As at today there is no sense having a to-ing and fro-ing about this specific issue.

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#8

I’m not that familiar with it but if I had to comment I would like to say that AD and dementia, if they’re caused by E4 alleles or the risk factors that are under lifestyle control, those cases wouldn’t be aging either, and it could be a substantial amount of cases.

Based on what, do the AD prevalence reach 100% in supercentenarians?

I didn’t, that’s why I said exposure (or lifestyle) and time.

Aging is a thing of course, and it is causing many diseases, and is limiting the maximum lifespan in humans, maybe the problem lies in anything that doesn’t limit maximum lifespan on its own as well in a population?

Now that I think about it there might be an atherosclerosis process related to aging but that isn’t the cause for the disability and death within a normal lifespan as calcified plaque on a CAC scan is guaranteed given a long enough lifespan, while we would expect outliers here if it wasn’t aging. But correct me if I’m wrong.

#9

I was more or less agreeing in many words. I think we have a similar viewpoint.

#10

It can’t be, it’s typically considered to be the process that can’t be changed and is inevitable, and any disease someone have can be explained away as aging, that they couldn’t do anything to change it. It’s what causes the maximum human lifespan at currently 122 years. You can prevent the majority of ASCVD in a normal lifespan, it doesn’t fit the criteria (What we understand to be ASCVD is developing it in a normal lifespan).

The heart aging would cause the heart disease by minuscule changes, possibly compounding, over a long period? The straw that breaks the camel’s back is when the disease occurs.

Yeah, that’s the idea, is there a single cause underlying the aging of all systems, or is just all systems separately aging in their own ways?

Thoughts about the above?

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#11

Supercentenarians still die of something eventually. It’s your weakest link that gets you, barring the proverbial bus. So perhaps if whatever killed them were removed or postponed AD / dementia would still eventually progress. Not saying this is the case. I’m agnostic. I’m saying it could very well be the case.

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#12

For another viewpoint, see Mikhail Blagosklonny’s classic paper “Aging and Immortality: Quasi-Programmed Senescence and Its Pharmacologic Inhibition” at https://www.tandfonline.com/doi/pdf/10.4161/cc.5.18.3288. He argued that (i) in a world of predators, pathogens, etc. evolution has selected for early survival and reproduction (versus longevity), (ii) there is a “developmental program” in our biology to accomplish this, and (iii) with little selection pressure to alter or stop this program, it just continues, yielding “cellular hyper-function” and senescence.

#13

Suppose you ran an experiment with a diverse set of mice and tracked lineages. Feed them in some reasonable way, and allow the most natural environment you can within a lab setting.

Track the death ages of each mouse, and eliminate all offspring descended from parents who did not live past the median (or some other percentile) of their generation.

If you do this for a large number of generations, would you expect to see the length of that percentile cutoff rise? In other words, if you applied a selective pressure on longevity, could you increase lifespan over generations?

If that worked, could you then identify genetic differences between the long-lived and original or wild type mice that would be systematically associated with longevity? And could you test that relationship by trying to unregulated or down regulate those genes in regular mice to see if it influenced their lifespan or had other downstream effects you could study to understand the mechanism mediating the increase in lifespan?

It seems so simple. I don’t know why something like this has not been done already. They did that experiment domesticating foxes and learned some interesting stuff.

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#14

Absolutely agree on this. I don’t think it would take that many generations to extend life, but what would we be giving up? Probably something that could extend life under different environmental conditions. So we get a 150 year lifespan under room temperature relatively clean conditions. But usually there’s a catch.

I agree this would be a great project. Just start breeding the longest lived mice.

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#15

I like living at room temperature under relatively clean conditions. :joy:

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#16

You’d probably hit a wall quickly unless you breed like a billion mice.

#17

Is that based on anything other than a kind of inherent skepticism of anything that seems too good to be true?

#18

Because mice are little cancer factories and if breeding the right mutations to successfully suppress cancer formation was feasible, therapies addressing those would’ve already been found after decades of research and trillions of dollars of funding.

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#19

It would be fun to see where the wall is. Say there was a yearly prize of $50000 for the longest lived mouse of the year. Of course somebody would figure out how to cheat by using the naked mole or something, but even using just mice I think you could be very surprised by the extension and short time to get there.

I actually have some experience here, unlike almost everything else we talk about. I bred Nubian goats for milk supply for about 20 years. In the end I had the top buck in the country and several on the elite list. Never made a dime, and my help all graduated and left so ended up quitting. Now my wife does it and makes cheese, but does not compete. The winningest most milky doe had huge vet bills. Her immune system was awful.

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