70 replies to this topic

[AussieVampire]

Mathematical models show even immortal populations are outcompeted by aging populations due to enhanced evolvability.

As for survival this may affect many organisms but fittest mature organism is likely to outcompete immature organism if it is not subject to aging. Aging starts causing reduction in fitness from the moment of age of sexual reproduction even months or years after there is already notable decline that adversely affects survival. It is not just dying of old age decline in fitness starts from early adulthood.

 

So aging is more of a byproduct of the evolved complexity that makes an organism more competitive for survivability/reproduction.

I think that evolutionary pressure is making organisms evolve complex new systems without the afterthought of Longevity because they die at some average age from environmental causes. This was true for most of our evolutionary past as well.

If you prevented a group organisms from breeding until slightly after the average age of fertility drop off and only let the highest performing ones breed. I believe there would also be evolutionary pressure towards Longevity features for our complex systems.

I still think it's a lack of evolutionary pressure towards longevity than an intentional programmed aging. Programming aging into an organism independent of anything else has no benefit whereas if it's a byproduct of performance with no afterthought it makes much more sense.

[AussieVampire]

So aging is more of a byproduct of the evolved complexity that makes an organism more competitive for survivability/reproduction.

I think that evolutionary pressure is making organisms evolve complex new systems without the afterthought of Longevity because they die at some average age from environmental causes. This was true for most of our evolutionary past as well.

If you prevented a group organisms from breeding until slightly after the average age of fertility drop off and only let the highest performing ones breed. I believe there would also be evolutionary pressure towards Longevity features for our complex systems.

I still think it's a lack of evolutionary pressure towards longevity than an intentional programmed aging. Programming aging into an organism independent of anything else has no benefit whereas if it's a byproduct of performance with no afterthought it makes much more sense.

Further thought on this

I agree now aging may actually be programmed into us with evolutionary intent. Aging starts to accelerate after development has ceased. This must be because increased proliferation increases risk of age related disease as every time a cell divides it's prone to producing errors (DNA Damage) which can lead to disease/cancer.

So it's a balancing act between programmed cell death or cancer.

This is why I think that extending telomeres in mice only increases maximum lifespan and not mean life span. Even though programmed cell death has been delayed and cells likely proliferate at a greater rate for longer, the rats are still subject to age related disease due to DNA damage and are now at greater risk of dying from that than too many cells reaching the end of their programmed lifespan.
 

[Castiel]

Further thought on this

I agree now aging may actually be programmed into us with evolutionary intent. Aging starts to accelerate after development has ceased. This must be because increased proliferation increases risk of age related disease as every time a cell divides it's prone to producing errors (DNA Damage) which can lead to disease/cancer.

So it's a balancing act between programmed cell death or cancer.

This is why I think that extending telomeres in mice only increases maximum lifespan and not mean life span. Even though programmed cell death has been delayed and cells likely proliferate at a greater rate for longer, the rats are still subject to age related disease due to DNA damage and are now at greater risk of dying from that than too many cells reaching the end of their programmed lifespan.

What I dont know is how cancer superimmunity fares into this. It is known that telomerase positive is seen in many ageless species. Telomerase positive also immortalizes and rejuvenates cells and tissues. Yet cancer superimmunity was found in mice and in humans and potentially other species.

Im not sure what the limits of cancer superimmunity are, are there cancers that can evade such? What about ageless animals do they have cancer superimmunity?

Would cancer superimmune organisms become biologically immortal if made telomerase positive?

[QuestforLife]

As I see it, evolution is just the result: did your (different) genes result in more or less surviving offspring? This could be achieved any which way. You could have limitless proliferative ability in all your cells. You could have telomerase locked down from the fetus stage (humans). 

 

It is not clear to me what is meant by cancer superimmunity? You could argue that humans are super immune in comparison to mice, for example.

 

I think Charles Brenner is basically right in his criticism of the longevity space. Ten years ago I was sure that life extension would become main steam. Now that it has, it is very disappointing to see that it is fully of hacks and charlatans.  I suppose I shouldn't be suprised given we are talking about ageing. So Brenner is right to call them out. In comparison to the increase in publicity, the advances into understanding (and addressing) ageing has been very limited in the last 10 years. There is always the chance of a breakthrough, of course, and more people  being involved makes that more likely. But right now we still have a bunch of biochemical theories, none of which has robustly demonstrated they are correct, and which don't at present fit very well together.    

[Castiel]

https://www.huffpost...nt-di_b_5472369

That is what I mean by cancer superimmunity. Something not all humans have.

A transplant from a superimmune humans immune cell into a cancer patient with late stage malignant metastastic cancer which has evaded all treatments and the immune cells completely wipe all traces of cancer.

I suspect this is how some centenarians can smoke 2 packs a day and be cancer free. They get cancer after cancer but their immune system eradicates them. Of course as mentioned this is not something all have.

[QuestforLife]

https://www.huffpost...nt-di_b_5472369

That is what I mean by cancer superimmunity. Something not all humans have.

A transplant from a superimmune humans immune cell into a cancer patient with late stage malignant metastastic cancer which has evaded all treatments and the immune cells completely wipe all traces of cancer.

I suspect this is how some centenarians can smoke 2 packs a day and be cancer free. They get cancer after cancer but their immune system eradicates them. Of course as mentioned this is not something all have.

Thanks for that, very interesting. This actually makes me depressed. How do we cure ageing when the system doesnt want to?

In some ways I wish Cui had stuck with mice. How long does a cancer immune mouse live?

A other example of the ability of the system to block progress. I've done research and found there is one lab in The US that can extract telomerase positive adult stem cells from humans that can divide indefinitely and repair any organ damage. But all other labs are only setup for induced pluripotent stem cells and no one is interested in replicating results that, if true, could completely change the conversation on why we age.

Like I said, depressing.

Edited by QuestforLife, 27 February 2025 - 07:14 PM.

[osris]

Science works because it has checks and balances. If you take away those checks and balances, you risk turning science into pseudoscience.

 

The scientific community reviews the work of its scientists, as published papers are scrutinised widely. And when a scientist or research group submits an application for a research grant to perform a study, that application is carefully scrutinised by the grant awarding body, and only if the ideas seem sound will funding be awarded.

 

Most professional scientists know that it is extremely difficult to get funding for a study you want to conduct, as there is so much competition from other scientists, who each want a grant for their studies. But there is only a finite amount of funding available. So in general, the funding goes to the scientists with what appears to be the best ideas (although there can be ideological bias in funding bodies, which favour some avenues of research over others, so sometimes great scientific ideas struggle to get funding).

 

But with longevity research, you are by-passing these checks and balances, because you are often not awarded your research grants from scientific funding bodies, but directly out of the pockets of the super rich, who are happy to pay $billions even for the remote possibility of 10 years extra life. Thus this corrupts the normal checks and balances in science, and allows hyperbolic statements to flourish. 

 

This is why in longevity and anti-ageing research, science often blurs into pseudoscience.

 

You make some good points, but I think this take on longevity research is a bit too black-and-white. There’s definitely hype and sketchy claims in the space—just like with any field that has big money and big promises attached. But that doesn’t mean longevity science itself is pseudoscience.

 

First off, private funding isn’t automatically bad. If anything, traditional research funding is ridiculously slow and conservative. Grant bodies tend to favor safe, incremental studies over high-risk, high-reward research. That’s why we see so many aging-related breakthroughs (like senolytics, partial reprogramming, and rapamycin trials) coming out of labs backed by private money. Without that funding, a lot of these ideas wouldn’t even get off the ground.

 

Serious longevity research does have checks and balances. Legit studies still go through peer review, clinical trials, and regulatory hurdles before they turn into real treatments. The problem isn’t that longevity science is inherently becoming pseudoscience; it’s that the hype machine (especially from startups looking for investors) sometimes makes things sound way more advanced than they actually are. That’s a messaging problem, not a science problem.

 

Bottom line: Sure, there’s BS in the longevity space, just like in any emerging field. But dismissing the entire thing as compromised because of private funding ignores the fact that some of the most promising research wouldn’t happen otherwise. The key is to stay skeptical, look at the actual data, and separate real science from marketing fluff.

[osris]

I don't believe this money will hasten progress, because longevity research is completely clueless as to the causes of chronic diseases and cancers, which are the factors which kill the vast majority of people.

 

Very few people die of natural old age; most die of a disease. Thus if you want to increase human lifespan, you need to focus on the (currently unknown) causes of disease, and then try to prevent or cure disease.  Longevity researchers seem to have their heads in the sand regarding this fact.

 

 

If it were not for disease, most humans would probably live to their natural lifespan of around 120 years. It is pointless trying to extending this 120 year lifespan, as longevity researchers attempt to do, if most people are killed long before 120 by a disease, often in their 60s, 70s or 80s.

 

Also, far more protracted human suffering occurs because of chronic diseases than because of death. Death may actually be the passage to a higher and more blissful state of existence, if you believe that the human soul is extra-temporal and exists eternally, so we cannot say whether death is a good or bad thing. But I think most people would agree that the suffering and loss of quality of life caused by chronic diseases is definitely a bad thing.

 

If the money possessed by the super rich went into studying the currently unknown causes of disease, it would be a far more efficient means to extend the lifespan, healthspan and quality of life of humanity.

 

 

 

 

Some billionaires , especially the ones who made their money from science and technology, may have a reasonable sense of what medical technologies are a viable investment.

 

I admire what Bill Gates does with his money, charitably giving $billions to the health technology sector, especially to fight infectious diseases in the third world. Gates has a good understanding of medical technologies, and spends his money wisely. He's not gullible, and has a knack for knowing when some medical tech idea is likely to work.

 

But I am not sure if engineers like Elon Musk or former physicist like Jeff Bezos have a good grasp of biology and medicine. Material engineering is a very different discipline to biology. Building solar cells, electric cars and rockets does not provide any understanding of the biological sciences.

 

And certainly the corrupt billionaire oligarchs from places like Russia, who make their money effectively by being gangster leaders of a state mafia, do not have much grasp on medical science. 

 

 

 

I get what you’re saying, but I think you’re misunderstanding what longevity research is actually about. It’s not just trying to push lifespan beyond 120 years while ignoring diseases—most of the serious work in this field is actually focused on preventing and reversing age-related diseases before they happen.  

 

You mention that most people don’t die of “old age” but of diseases like cancer, heart disease, and neurodegeneration. That’s *exactly* why longevity research matters. The reason these diseases are so common is because aging itself creates the conditions that make them more likely—cellular damage, loss of regenerative capacity, immune dysfunction, etc. If we can slow, stop, or even reverse some of these underlying aging processes, then we’re effectively preventing the biggest killers of humanity at their root, rather than just treating the symptoms after they show up.  

 

Think about something like senolytics, which target senescent (dysfunctional) cells that build up as we age and drive inflammation, cancer, and organ decline. Or partial cellular reprogramming, which has been shown to reverse biological aging in cells and tissues. These aren’t about “escaping death”; they’re about maintaining health *so* we don’t have to spend the last decades of life suffering from chronic disease.  

 

And sure, some people believe death leads to something better, but even if that’s true, I doubt most people would want to spend their last 20-30 years battling Alzheimer's, diabetes, arthritis, and multiple organ failures before getting there. Extending healthspan—keeping people functional and disease-free for longer—is something just about everyone can get behind.  

 

So rather than being “clueless” about disease, longevity researchers are actually tackling it at its most fundamental level. If they succeed, we’re not just talking about a longer lifespan, but a world where people stay healthy into their 90s and beyond instead of spending decades in decline. That seems like money well spent to me.

[osris]

The argument I presented above is different to Dr Brenner's argument. Brenner is calling bullshit on some (not all) of the claims of anti-ageing researchers. 

 

 

My argument is a far more serious criticism of anti-ageing research: my argument is that the whole life extension field is fundamentally flawed, because of the fact that few people actually die by reaching their natural lifespan of about 120 years; rather, the vast majority die of a disease. Diseases kill most of us, not ageing. 

 

Disease is the elephant in the room that anti-ageing researchers refuse to accept or discuss.

 

I suspect that these researchers and the billionaires who fund them may be healthy at present, and like most human beings with natural optimism, don't conceive of the possibly that they may be hit with a nasty disease 10 years hence. Thus they think that their death will come via ageing; but in all probably, their death will come from a disease that they contract at some point in their life. 

 

 

 

In all your reading of biomedical science, have you ever found any research from the anti-ageing camp that has advanced the understanding of what causes disease, how to prevent disease, or how to cure disease? 

 

I've been reading biomedical science for 15 years now (though my education was in mathematics and physics), and I've seen very little from the life extension field that has had any bearing on understanding diseases.

 

I don't think extending telomeres will prevent disease, for example. Even the antioxidant theory of ageing is not relevant to preventing disease: there are review studies which show that antioxidant supplements actually shorten lifespan, not extend it. 

 

 

 

My view is that longevity researcher need to change tack: they need to address the elephant in the room, and start looking at how they can prevent disease.

 

I think there’s a fundamental misunderstanding here about what longevity research is actually trying to achieve. It’s not about extending life for the sake of it, nor is it ignoring disease. In fact, longevity researchers are directly tackling the causes of age-related diseases—and many are trying to address those underlying mechanisms that make us vulnerable to conditions like cancer, heart disease, and neurodegeneration.

 

You’re right that most people die from diseases, but those diseases are often the result of aging itself. We know that aging causes a breakdown in cellular function, weakened immune responses, and an accumulation of damage in tissues—factors that increase the likelihood of developing things like cancer, Alzheimer's, and cardiovascular diseases. So, in many ways, the goal of longevity research is to prevent the diseases that arise from aging, not just try to add more years to life without quality.

 

For example, researchers are studying things like senolytics (drugs that clear out damaged, senescent cells) which directly prevent chronic diseases like heart disease and cancer by targeting one of the key drivers of aging. There’s also mTOR inhibitors like rapamycin, which show potential in preventing diseases like cancer and extending healthspan. Cellular reprogramming is being explored to reverse the effects of aging at a cellular level, potentially restoring the function of tissues and organs that would otherwise succumb to age-related diseases. These aren’t just about living longer—they’re about living healthier for longer and preventing the diseases that kill us in our 70s, 80s, or 90s.

 

And regarding telomere length, it’s not just a matter of adding years to life. The research is exploring how telomere shortening contributes to cellular aging, and by understanding this process, scientists hope to find ways to delay age-related diseases. Antioxidants may not be the holy grail, but the right combination of lifestyle, diet, and therapeutic approaches can still have an impact.

 

In short, longevity researchers are very much aware of the importance of disease prevention—they’re not ignoring it. In fact, the whole field is focused on stopping the diseases of aging before they even start. So while your point about disease being the primary killer is valid, longevity science is addressing that issue by targeting the underlying mechanisms that make diseases more likely as we age. It’s about tackling the root cause—aging itself—and preventing diseases as a result.

 

It’s not a simple “extend lifespan” approach, but a more holistic attempt to improve healthspan and reduce the burden of chronic diseases.

[osris]

This is certainly an interesting development. 

 

Though even if we could slow or reverse ageing, would this actually extend human lifespan, when the reality is that almost everyone dies of a disease, rather than dying of ageing. 

 

The only people who die of ageing are those rare individuals who reach around 120, which is about the natural human lifespan. These people may have avoided all the killer diseases, and thus are the only people who die of old age.

 

But for the rest of us, we all die of disease. If you look at the statistics for causes of death, you find that heart diseases, strokes, cancers, neurological diseases, dementia, diabetes, kidney diseases, lung diseases, etc are what kill people, not ageing. 

 

Thus if you want to extend lifespan, your first focus should be on preventing or curing disease, not slowing ageing.

 

 

A disease process once started slowly destroys the body, even in young people who are not aged. You can have any of the diseases I listed when you are young and at your peak physical health.

 

For example, people are hit with multiple sclerosis in their 20s. People are hit by diabetes in their teens. Disease is nothing to do with ageing. Disease is an affliction which hits the body, and once a disease starts, this mysterious process is generally progressive.

 

 

 

So what we need to do is understand what causes disease. 

 

20 years ago, it was believe that all diseases would have genetic causes. This is why so much money was spent on the Human Genome Project, to sequence all human DNA, because back then scientists believed that bad genes were the cause of disease. 

 

But they were wrong: once the Human Genome Project was completed in 2003, it soon became apparent that genetics had not much bearing on disease, and that bad genes were not actually the cause of disease. 

 

So we urgently need to discover what triggers the disease process in the body, because it is disease, not ageing, that prematurely kills almost everyone.

 

I get where you're coming from, but I think there’s a misunderstanding about the relationship between aging and disease. You're right that most people die from diseases, but those diseases are deeply connected to aging itself. Aging doesn’t just happen in isolation—it’s a process that affects every cell, organ, and system in the body, setting the stage for diseases like heart disease, cancer, diabetes, and neurodegeneration.

 

It’s true that some diseases hit younger people, like multiple sclerosis or type 1 diabetes, but these are the exception rather than the rule. For most people, aging itself is a major contributor to the chronic diseases that cause death. When we age, our bodies become less efficient at repairing damage, maintaining cellular function, and defending against things like cancer or cardiovascular issues. This process of deterioration is what ultimately makes us more vulnerable to disease as we get older.

 

Take something like senescence—the process where damaged cells stop dividing and accumulate in tissues as we age. These senescent cells drive chronic inflammation and contribute to diseases like cancer, atherosclerosis, and neurodegeneration. Targeting this process, through treatments like senolytics, could reduce the risk of these diseases before they even develop. It's not just about living longer; it's about living healthier and reducing the likelihood of these diseases taking hold as we age.

 

Yes, the goal should be to understand and cure disease, but longevity research is addressing why those diseases emerge in the first place. By slowing or reversing aging processes, we can reduce the risk of the diseases you mentioned in the first place. If we can prevent the age-related decline in immune function, cellular regeneration, and tissue repair, we’re essentially preventing the diseases that kill most people—heart disease, diabetes, cancer, and more.

 

And as for the Human Genome Project, you’re correct that it wasn’t the magic bullet some expected. But genomics is still very important in understanding how genetic predispositions interact with environmental factors to contribute to disease. That said, a huge focus in aging research today is on epigenetics—how our environment, lifestyle, and aging processes influence gene expression. These aren’t just “bad genes”; they’re changes to our DNA and cellular function that happen over time, causing diseases that could be prevented with the right interventions.

 

So, rather than being separate areas of focus, aging and disease are closely intertwined. Tackling aging itself could be the key to preventing the diseases that kill most of us. It’s not about ignoring disease; it’s about targeting the root causes of those diseases by understanding and slowing aging.

[osris]

In some diseases, ageing may be a risk factor for contracting them. As you point out, the immune system becomes less effective with age (immunosenescence), so can lead greater incidence of cancers and fatal infections such as pneumonia in older people.

 

Though immunosenescence may itself be a disease it its own right (immunosenescence has been linked to the persistent cytomegalovirus infection found in most adults for example), to some extent.

 

 

However, other diseases like type 1 diabetes occur early in life, with the average age of incidence being 13 years. And for multiple sclerosis, this typically begins from between the ages of 20 and 50, which is before any major ageing takes place. Crohn's disease, cystic fibrosis, epilepsy are more examples of diseases which occur in young people. So you do not have to be old to get a chronic disease.

 

The reason that some diseases are more common later may relate to the infectious pathogen theory of disease: one theory posits that most chronic diseases will turn out to be caused by the persistent microbes (viruses, bacteria, etc) that live in our bodies. We catch new microbes all the time, and so the longer we live, the more microbes we have in our body cells and tissues. Many of these microorganisms have been linked to chronic disease.

 

So some diseases may occur later in life because of a combination of ageing, immunosenescence, and the ever-increasing microbial load harboured in our bodies as we get older. 

 

That’s an interesting point, and I’d agree that the accumulation of persistent infections and microbial load over time is a significant factor in many chronic diseases. However, I’d argue that this isn’t separate from aging—it’s actually one of the processes that aging research is trying to address.

 

For example, immunosenescence makes us less capable of controlling persistent infections like cytomegalovirus (CMV), Epstein-Barr virus, and other latent pathogens. These infections don’t just sit there harmlessly; they actively shape immune aging, increasing inflammation and contributing to diseases like cardiovascular issues, neurodegeneration, and even some cancers. If we can reverse or delay immunosenescence, we might be able to mitigate these downstream effects.

 

You’re right that some diseases strike early in life—type 1 diabetes, MS, Crohn’s, etc—but these are the exceptions rather than the rule. The vast majority of chronic diseases increase in prevalence with age, and even the ones that start earlier often get worse due to aging-related changes. Even in conditions like MS or Crohn’s, older patients tend to have worse outcomes due to the additional burden of immune dysfunction and systemic aging.

 

The infectious pathogen theory of chronic disease is fascinating, and some aging researchers are looking into it. If persistent infections are a major driver of aging-related diseases, then targeting aging itself—whether by improving immune function, reducing inflammation, or even using senolytics to clear infected senescent cells—could help prevent many of these diseases from ever emerging.

 

So rather than seeing aging and disease as two separate things, I’d say they’re interconnected. Aging is what makes us more vulnerable to the accumulation of infections, inflammation, and chronic disease. That’s why longevity research isn’t just about extending lifespan—it’s about tackling the mechanisms that make us susceptible to disease in the first place.

Edited by osris, 09 March 2025 - 05:53 PM.