56 replies to this topic

[Hip]

Longevity skeptic and biochemist Dr Charles Brenner believes life extension is about as likely as the existence of the tooth fairly.

 

Brenner has been attending the largest longevity conferences with one main purpose: to point out that some of the longevity speakers are full of it.

 

Brenner is throwing cold water on several anti-ageing scientists, accusing them of hyping various fountains of youth, despite limited evidence for these therapies.

 

Basically, Dr Brenner is calling bullshit on the idea of extending human lifespan.

 

At best, Brenner says, scientists can develop therapies that maintain the health of older people and help keep them out of the hospital.

 

 

 

 

Sources:

 

Repairing Cells and Longevity Myths with Dr Charles Brenner

 

The Longevity Skeptic — biochemist calls BS on extending human lifespan

 

[hplus]

Is Dr. Brenner's argument also grounded in scientific evidence?

[Hip]

Is Dr. Brenner's argument also grounded in scientific evidence?

 

I have not looked into the science, as no doubt it is complicated, and would require a great deal of reading to get abreast of it. In the 2nd article it refers to sirtuins, and the longevity claims behind these. So one would have to know about such things to have an informed opinion.

 

 

But certainly you don't need to have in-depth knowledge to know that some statements made by longevity researchers are total hyperbole. For example, Aubrey de Grey's statement that "the first person to live to 1,000 years of age has already been born" is just laughable. The idea that medical science is going to advance so fast within a few decades that everyone will be living to 1,000 is preposterous!

 

This sort of hyperbole comes from the fact there are a lots of super-rich people with $billions, who suddenly realise that they are going to die before they can spend and enjoy the insane amount of wealth they have. The first article posted above says that "investments in longevity startups are projected to increase from $40 billion to $600 billion over the next three years". Much of this money is coming from the super wealthy, trying to buy their way to immortality. 

 

So that is a huge amount of money available for longevity researchers, more than half a $trillion, and so to grab some of that cash, researchers and start-up companies are naturally going to concoct all sorts of hyper-exaggerated claims about their life extension ideas. Thus that money creates a dishonest environment where longevity claims whose science is either highly dubious or totally bullshit will be nevertheless awarded millions or billions in research funding. These longevity researchers are on the gravy train. 

 

The rich and powerful have often sought eternal life: the Chinese emperor Qin Shi Huang famously drank liquid mercury, on the belief it would give him eternal life, and slowly poisoned himself to death in 210 BC.

Edited by Hip, 07 June 2023 - 03:25 PM.

[hplus]

In my opinion, political ideologies should not be brought into scientific discussions. Nonetheless, I am intrigued to know Dr. Brenner's take on the recent experiments involving partial reprogramming that resulted in the rejuvenation of mice.

[Hip]

In my opinion, political ideologies should not be brought into scientific discussions. Nonetheless, I am intrigued to know Dr. Brenner's take on the recent experiments involving partial reprogramming that resulted in the rejuvenation of mice.

 

Which political ideologies? I am talking about how hyperbole-spouting researchers, claiming they have the secret to eternal life, are fleecing the super rich of their $billions.

Edited by Hip, 07 June 2023 - 03:29 PM.

[hplus]

Ideologies like this:

This sort of hyperbole comes from the fact there are a lots of super-rich people with $billions, who suddenly realise that they are going to die before they can spend and enjoy the insane amount of wealth they have.

 

 

When refuting scientific theories, it is important to focus solely on the science and avoid discussions about "$billions."

 

So is it hyperbole-spouting when scientists state that they can reverse the age of a mouse?

Edited by hplus, 07 June 2023 - 03:38 PM.

[Hip]

When refuting scientific theories, it is important to focus solely on the science and avoid discussions about "$billions."

 

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.

Edited by Hip, 07 June 2023 - 03:59 PM.

[Hip]

Researchers are optimistic about recent efforts to delay the effects of aging and, perhaps, extend life spans.

 

But at the same time, the scientific community is wary of how quickly these findings are packaged and resold by companies promising a fountain of youth.

 

“It’s probably worse today than it’s ever been,” said Dr. S. Jay Olshansky, a professor in the School of Public Health at the University of Illinois at Chicago and a research associate at the Center on Aging at the University of Chicago. “As soon as the scientists publish any glimmer of hope, the hucksters jump in and start selling.”

 

Source: Science (and Quacks) vs. the Aging Process — New York Times.

[hplus]

First of all, we should express gratitude towards the $billionaires for their substantial investments in geroscience in recent years, as it will significantly hasten progress. Consequently, those of us who aren't $billionaires do have a fair chance of being spared from a painful death caused by the aging disease.

 

Secondly, the fact that $billionaires invested $billions in geroscience in recent years is the best sign that scientists are very close to a breakthrough. $Billionaires are $bilionaires for a very good reason. They know how to invest to make more $billions.

 

Thirdly, if Dr. Brenner's objections stem solely from a socialist ideology and lack any substantial scientific evidence countering recent advancements in geroscience fields such as partial reprogramming, senolysis, or heterochronic parabiosis, we can rest assured that a solution to this devastating disease may soon be discovered.

Edited by hplus, 07 June 2023 - 04:51 PM.

[Hip]

First of all, we should express gratitude towards the $billionaires for their substantial investments in geroscience in recent years, as it will significantly hasten progress. Consequently, those of us who aren't $billionaires do have a fair chance of being spared from a painful death caused by the aging disease.

 

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.

 

 

 

$Billionaires are $bilionaires for a very good reason. They know how to invest to make more $billions.

 

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. 

 

 

Edited by Hip, 07 June 2023 - 05:39 PM.

[hplus]

I highly recommend dedicating at least 2 hours daily for studying biosciences and geroscience. After a year, it will become apparent how flawed Dr. Brenner's argument is.

[Hip]

I highly recommend dedicating at least 2 hours daily for studying biosciences and geroscience. After a year, it will become apparent how flawed Dr. Brenner's argument is.

 

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.

[gamesguru]

The general belief is that people born today won't live forever. They might, through medical advances, make it to 120 on average and 150 max. Medical advances appear to be following the law of diminishing returns or low-hanging fruit. The burden of proof ought to be on the optimists to explain how cures to all the causes of aging clearly are within reach in our lifetimes (rather than the burden falling on the skeptics to explain why they likely are not).

 

Last I checked, there have been no profound developments in the past 10 years in any of the over dozen theories on aging.

 

Solving aging also requires, as a subset, the solution of all other causes of biological mortality, such as ALS (Lou Gerhig's disease), as well as congenital conditions (such as Angelman syndrome). And while solutions to these problems may come within our lifetimes, we cannot, given the current political, economic, environmental, and intellectual atmosphere, think them likely or imminent.

[Mind]

Based upon my subjective experience, I am somewhat sympathetic to Dr. Brenner's views. I have been advocating for rejuvenation and raising money for such efforts for over 20 years now - and for the 20 years prior to that, there were other advocates pushing hard for more research and promising therapies.

 

Yet we have nothing. Nothing that has been robustly proven to rejuvenate the human body. Nothing widely available and successful.

 

Nowadays, I am more inclined to support biohackers. They seem to be getting better results and are doing more objective measurements.

 

The advance of AI throws a wild card into future projections. If leveraged in a positive ethical manner, advanced AI should be able to bring about rejuvenation a lot quicker.

[Harkijn]

I think the rejuvenation crowd needs an 'enemy'like dr. Brenner to keep their feet fimly on the ground, as many claims are unsubstantiated and 'clocks' are founded on quicksand.

[hplus]

Based upon my subjective experience, I am somewhat sympathetic to Dr. Brenner's views. I have been advocating for rejuvenation and raising money for such efforts for over 20 years now - and for the 20 years prior to that, there were other advocates pushing hard for more research and promising therapies.

 

Yet we have nothing. Nothing that has been robustly proven to rejuvenate the human body. Nothing widely available and successful.

 

Nowadays, I am more inclined to support biohackers. They seem to be getting better results and are doing more objective measurements.

 

The advance of AI throws a wild card into future projections. If leveraged in a positive ethical manner, advanced AI should be able to bring about rejuvenation a lot quicker.

 

For two decades, scientists have been pursuing a faulty theory, believing that aging is caused by the accumulation of damage. However, the discovery of Shinya Yamanaka has changed everything. We now know that cells can be rejuvenated through reprogramming, which means that aging is actually programmed and damage accumulation is merely an effect. And with Belmonte's successful demonstration of reversing age in mice through partial reprogramming, a cure for aging is now within reach. We already have the knowledge to achieve this goal; the next step is to ensure its safety for human use.

[Hip]

 

For two decades, scientists have been pursuing a faulty theory, believing that aging is caused by the accumulation of damage. However, the discovery of Shinya Yamanaka has changed everything. We now know that cells can be rejuvenated through reprogramming, which means that aging is actually programmed and damage accumulation is merely an effect. And with Belmonte's successful demonstration of reversing age in mice through partial reprogramming, a cure for aging is now within reach. We already have the knowledge to achieve this goal; the next step is to ensure its safety for human use.

 

 

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.

[hplus]

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.

 

You are confusing "dying of old age" with "dying of aging." 

 

When a person dies of old age, it is usually due to the failure of a vital organ that can no longer be repaired. This is often the case for those who live to be over 100 years old.

 

On the other hand, dying of aging in today's society means that a person dies from a disease that was caused by aging, such as heart disease, cancer, diabetes, or strokes. These diseases are considered to be diseases of aging because the risk of developing them increases exponentially with age.

 

For example, one of the reasons why the risk of developing cancer increases with age is because the aging immune system is less effective at clearing cancerous cells from the body. If a cure for aging is found, the number of people who die from cancer and other diseases of aging will decrease dramatically.

 

Most geroscientists widely accept the belief that discovering a cure for aging would significantly prolong human lifespan.

Edited by hplus, 10 June 2023 - 06:15 PM.

[Hip]

On the other hand, dying of aging in today's society means that a person dies from a disease that was caused by aging, such as heart disease, cancer, diabetes, or strokes. These diseases are considered to be diseases of aging because the risk of developing them increases exponentially with age.

 

For example, one of the reasons why the risk of developing cancer increases with age is because the aging immune system is less effective at clearing cancerous cells from the body. If a cure for aging is found, the number of people who die from cancer and other diseases of aging will decrease dramatically.

 

Most geroscientists widely accept the belief that discovering a cure for aging would significantly prolong human lifespan.

 

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. 

Edited by Hip, 10 June 2023 - 06:56 PM.

[hplus]

Of course, I'm referring to type 2 diabetes here. While the other diseases you mentioned are not significant in terms of numbers compared to the typical aging-related diseases. Hence, I'm curious why you bring them up here.

 

I don't find the infectious pathogen theory of disease convincing. The immune system becomes more efficient with exposure to different pathogens, and having a diverse microbiome, like in the gut, can lower the risk of cancer. Thus, having more species of bacteria and viruses is beneficial to the immune system.

 

Without going into the details here, we already have a good understanding of why the immune system is less effective at age. One reason is that the thymus shrinks as we age, which is genetically predetermined. Another cause is the accumulation of senescent cells that triggers chronic inflammation, keeping the immune system too occupied to detect every cancerous cell. The accumulation of senescent cells is also mainly programmed (Hayflick limit).

 

Partial reprogramming is effective because it resets the programmed causes of aging, including those previously mentioned. For instance, partial reprogramming extends telomeres, which lowers the accumulation of senescent cells.

 

But of course, this is just scratching the surface of the topic.

[gamesguru]

It doesn't matter if the "other" diseases are less common or significant. They are probably very significant to the families with members who have been afflicted. If you're going to cure aging and unnecessary human suffering, it requires the tremendous medical achievement of curing all disease, preventing all the causes of aging and biological suffering. This would ultimately include cosmetic fixes as well, such as impaired vision and cataracts, and not just be limited to big killers (heart disease, cancer, diabetes, etc).

 

So, you've identified the immune system as one of the organ systems which undergoes aging and results ultimately in the degredated performance and health of the human organism. And you've identified various weak points or mechanisms behind this decline, as well as potential solutions. But how effective are these solutions? Why does the thymus shrink? To what extent can telomeres be lengthened? Can the Hayflick limit be avoided? Are errors in DNA and mitochondrial dysfunction similarly reversible? What about the accumulation of senescent cells and other unwanted debris, AGEs, etc?

 

I agree this is just scratching the surface on the topic. But the deeper we delve, the murkier and less certain things will become.

[Hip]

I don't find the infectious pathogen theory of disease convincing.  

If you rule out the pathogen theory of chronic diseases, would you care to speculate on what factors cause the various diseases that blight human existence?

 

If you take a scientific perspective, every effect has a cause. Therefore, for a given disease to appear in a previously healthy body, there must be one or more causal factors. We already know that genes do not play a major role in disease (except in the small number of purely genetic diseases like say Huntingdon). So genes are not the elusive causal factor behind disease.

 

So I wonder what your view is on the factors which might cause disease. Have you had any thoughts on this?

 

 

 

The immune system becomes more efficient with exposure to different pathogens, and having a diverse microbiome, like in the gut, can lower the risk of cancer. Thus, having more species of bacteria and viruses is beneficial to the immune system.

 

In general the immune system does not become more efficient with increased exposure to pathogens; the opposite may be more the case. This in part is to do with immune evasion. 

 

No pathogen could survive long term in the body if it "played fairly" with the immune system: if microbes played fairly, the immune system would efficiently wipe out all micro-organisms.

 

The reason the immune system cannot wipe out most microbes is in part because all microbes engage in what are known as immune evasion strategies to avoid being killed by the immune system. These immune evasion strategies involve "hacking" into the the host immune system, and disabling it or thwarting immunity. Each microbe is able to successfully thwart or disable the immune system, for its own survival purposes.

 

I can give you many specific examples of immune evasion if you are interested. Every example involves chronic ongoing damage to the immune system.

 

Each virus and bacterium uses multiple ways of disabling immunity, otherwise they could not survive in our bodies. Immune evasion corrupts the proper functioning of the immune system, just like foreign state hackers interfering in elections can corrupt the democratic electoral process.

 

Microbes also hide from the immune system by living inside human cells, as an intracellular infection. This is another reason why the immune system cannot eradicate microbes from the body. And their present in our cells can lead to cellular dysfunction.

 

For example, it is well known that Epstein-Barr virus, which nearly all adults have in their bodies, lives inside the B-cells of the immune system (the cells that make antibodies). Some researchers believe that having EBV inside your B-cells predisposes you to autoimmune diseases, where you antibodies mistakenly start attacking your own tissues. Indeed, many researchers believe that an effective EBV vaccine would entirely wipe out certain autoimmune diseases like multiple sclerosis.

 

 

 

 

 

Edited by Hip, 10 June 2023 - 08:12 PM.

[Hip]

having a diverse microbiome, like in the gut, can lower the risk of cancer.

 

The reason that a diverse microbiome is healthier may be because the diversity helps keep the more pathogenic gut bacteria in check. Many gut bacteria are commensal organisms, that do no harm. But some gut bacteria are more pathogenic, especially when their populations start to grow disproportionately in relation to the other 300 to 500 bacterial species in your gut.  

 

For example, some strains of the common gut bacterium Escherichia coli make the toxin colibactin, which damages DNA and is linked to colorectal cancer. 

 

So if you had a dysbiotic overgrowth of such bacteria in your gut, it would be a greater cancer risk, compared to when there is less overgrowth and more microbial diversity. The microbial diversity helps crowd out the more pathogenic bacteria.

Edited by Hip, 10 June 2023 - 08:26 PM.

[hplus]

It doesn't matter if the "other" diseases are less common or significant. They are probably very significant to the families with members who have been afflicted. If you're going to cure aging and unnecessary human suffering, it requires the tremendous medical achievement of curing all disease, preventing all the causes of aging and biological suffering. This would ultimately include cosmetic fixes as well, such as impaired vision and cataracts, and not just be limited to big killers (heart disease, cancer, diabetes, etc).

 

So, you've identified the immune system as one of the organ systems which undergoes aging and results ultimately in the degredated performance and health of the human organism. And you've identified various weak points or mechanisms behind this decline, as well as potential solutions. But how effective are these solutions? Why does the thymus shrink? To what extent can telomeres be lengthened? Can the Hayflick limit be avoided? Are errors in DNA and mitochondrial dysfunction similarly reversible? What about the accumulation of senescent cells and other unwanted debris, AGEs, etc?

 

I agree this is just scratching the surface on the topic. But the deeper we delve, the murkier and less certain things will become.

Aubrey de Grey argued that the complexities of cell biology do not need to be fully understood in order to reverse aging. He suggested that repairing damage caused by the wear and tear of metabolism is sufficient. However, this argument is flawed. Repairing inner cellular damage requires intervention with biochemistry, which cannot be accomplished without a comprehensive understanding of the biochemistry in the entire cell. Unlike cars (Aubrey's favorite metaphor), where the molecules in the brakes do not affect the processes in the carburetor, essentially every molecule in a cell can interact with every other molecule. Therefore, repairing cell damage is far from trivial.

 

It was evident from the start that attempting to repair the damage caused by aging was a futile approach, which is why established bio scientists avoided delving into the topic. However, there has been a fundamental shift in our understanding since we now realize that aging is a programmed process. Therefore, it is now reasonable to argue that we do not need to comprehend the entire program in order to intervene.

 

Compare this to the program that runs this forum. When it comes to posting on this forum, you don't need to comprehend the forum software's code. Simply identify the appropriate form field to enter the text and the button to click to publish. You can trust this process for two reasons: you've done it many times before with consistent success (inductive reasoning) and you know that the developers who created the program wired the reply button to the publishing function (deductive reasoning).

 

This is exactly why researchers know that partial reprogramming resets the aging clock. The phenomenon has been observed numerous times and we know that these complex reset programs have been developed over billions of years of evolution. The key to unlocking this process is finding the correct transcription factors and knowing how to apply them. Although the mechanism behind these reset programs remains a mystery, their effectiveness is established.

 

And only these significant advancements in our scientific knowledge of the underlying causes of aging have led to an influx of funding in geroscience (and certainly not Dr. Brenner's conspiracy theory). Renowned scientists, including Nobel Laureates, are now dedicatedly working towards discovering a cure for this debilitating illness.

[hplus]

In general the immune system does not become more efficient with increased exposure to pathogens; the opposite may be more the case. This in part is to do with immune evasion. 

 

This is certainly wrong. All the infants that have been isolated during the pandemic from pathogens were in serious trouble when their untrained immune system was suddenly exposed to relatively harmless viruses and bacteria. The immune system, like any other organ, needs to be used in order to function properly. Use it or lose it. In order to maintain a healthy immune system, it is important to be regularly exposed to pathogens.

 

I'm not addressing your other comments on the immune system as they appear unrelated to the current topic. However, it's important to note that there is no evidence to suggest that pathogens cause diseases commonly associated with aging such as atherosclerosis, diabetes, or most cancers. However, the aging immune system likely plays a significant role here.

[gamesguru]

Aubrey de Grey argued that the complexities of cell biology do not need to be fully understood in order to reverse aging. He suggested that repairing damage caused by the wear and tear of metabolism is sufficient.

 

Do you have a quote on this. He is a pretty smart guy, though somewhat academically removed at this stage, so it is a bit surprising he would say epigentic aging is the only real cause (when we have evidence supporting over two dozen other theories). His recent publications seem heavily biased in favor of SENS. And while the SENS foundation may be non-profit, not all of his endeavors are.

 

Negligible senescence remains a theory, and one limited to a few simple species (e.g. quahog clam) with markedly repressed metabolism. Epigenetic aging and the clock has been studied in a few organ systems, but it is not ready for the prime time yet.

 

Afaik, the "effectiveness" is not established. And even if it were, that says nothing about how accessible the technology will be, or how many decades it will take to flush out.

 

While your analogy is helpful in understanding, I don't think it definitively proves anything about the world a posteriori. The body is a complex machine, just because it is supposedly "programmed" does not mean we can now reduce its complexity to that of a car repair. We have yet to fully decode this programmed process, or to devise tools which can intervene. And there may be much more going on that we need to understand for a full picture.

 

Regarding the debate between you and Hip, I have to side with him that THERE ARE OTHER THEORIES OF AGING! Besides the decline in immune function (which is likely multifaceted and difficult to explain), there is the burden of virus-mediated gene delivery (a process similar to lysogeny).

 

Pathogen Burden, Blood Biomarkers, and Functional Aging in Community-Dwelling Older Adults
https://pubmed.ncbi....h.gov/33640984/

 

Beware the ‘molecular parasites’ involved in aging and disease
https://www.brown.ed...-17/transposons

 

Humans are 8% virus – how the ancient viral DNA in your genome plays a role in human disease and development
https://theconversat...elopment-192322

 

While exposure to pathogens might be good for infants' immune systems, it's not clear that the stress of an infection has any benefits on someone who is 110 years old.

Edited by gamesguru, 11 June 2023 - 08:05 PM.

[Hip]

it's important to note that there is no evidence to suggest that pathogens cause diseases commonly associated with aging such as atherosclerosis, diabetes, or most cancers. However, the aging immune system likely plays a significant role here.

No evidence to suggest that pathogens cause the diseases commonly associated with ageing such as atherosclerosis, diabetes, or most cancers!?! 
 
How is it that you have missed the vast body of research which has associated these and many other chronic diseases to infectious pathogens?
 

Atherosclerosis is linked to cytomegalovirus, the bacterium helicobacter pylori, and the bacterium Chlamydia pneumoniae. 

 

Refs:

https://pubmed.ncbi.....gov/25834719/ 

https://pubmed.ncbi....h.gov/25725176/

https://pubmed.ncbi....h.gov/12468766/

 

Type 1 diabetes is linked to certain enteroviruses such as coxsackievirus B4, which infects and kills the insulin-producing beta cells of the pancreas. 

 

Refs:

https://pubmed.ncbi.....gov/21292721/ 

https://pubmed.ncbi.....gov/19266182/ 

https://pubmed.ncbi.....gov/18951821/ 

https://pubmed.ncbi....h.gov/17360338/

 

 

For any chronic disease or cancer you care to mention, you will find similar studies to these, in which infectious pathogens are found living in the diseased organs or tissues of a patient with a chronic disease. Now of course association does not prove causation, and more work is necessary to prove whether or not these pathogens found present in the diseases are indeed the cause of the disease, or just innocent bystanders.

 

But the statement that there is no evidence linking diseases of ageing to pathogens is not correct.

 

Don't worry though, because most longevity researchers are equally unaware about the pathogen connection to chronic disease. 

 

 

 

 

Still interested to hear your views on the factors which you think cause disease. You don't believe pathogens are responsible, so what factors do you think cause disease?

 

When you look into it, there is actually only a very limited set of factors external to the body that could cause disease. These factors include:

 

Environmental toxins, both manmade and natural

Radiations of various kinds, both manmade and natural

Medical drugs with adverse effects

Genetic factors

Epigenetic factors

Conditions during gestation 

Infectious pathogens (viruses, bacteria, fungi, parasites and archaea)

Diet and lifestyle factors

 

So if you are ruling out pathogens from disease aetiology, which of these other listed factors do you think precipitate disease?

 

Toxins? Well certainly there are a lot more of these in the environment since the Industrial Revolution; but people were still getting ill before industrialisation. 

 

 

Edited by Hip, 12 June 2023 - 04:05 AM.

[hplus]

Do you have a quote on this. He is a pretty smart guy, though somewhat academically removed at this stage, so it is a bit surprising he would say epigentic aging is the only real cause (when we have evidence supporting over two dozen other theories). His recent publications seem heavily biased in favor of SENS. And while the SENS foundation may be non-profit, not all of his endeavors are.

 

I didn't say anything about epigentic aging and Aubrey de Grey.

[hplus]

No evidence to suggest that pathogens cause the diseases commonly associated with ageing such as atherosclerosis, diabetes, or most cancers!?! 
 
How is it that you have missed the vast body of research which has associated these and many other chronic diseases to infectious pathogens?
 

Atherosclerosis is linked to cytomegalovirus, the bacterium helicobacter pylori, and the bacterium Chlamydia pneumoniae. 

 

Refs:

https://pubmed.ncbi.....gov/25834719/ 

https://pubmed.ncbi....h.gov/25725176/

https://pubmed.ncbi....h.gov/12468766/

 

Type 1 diabetes is linked to certain enteroviruses such as coxsackievirus B4, which infects and kills the insulin-producing beta cells of the pancreas. 

 

Refs:

https://pubmed.ncbi.....gov/21292721/ 

https://pubmed.ncbi.....gov/19266182/ 

https://pubmed.ncbi.....gov/18951821/ 

https://pubmed.ncbi....h.gov/17360338/

 

 

For any chronic disease or cancer you care to mention, you will find similar studies to these, in which infectious pathogens are found living in the diseased organs or tissues of a patient with a chronic disease. Now of course association does not prove causation, and more work is necessary to prove whether or not these pathogens found present in the diseases are indeed the cause of the disease, or just innocent bystanders.

 

But the statement that there is no evidence linking diseases of ageing to pathogens is not correct.

 

Don't worry though, because most longevity researchers are equally unaware about the pathogen connection to chronic disease. 

 

 

 

 

Still interested to hear your views on the factors which you think cause disease. You don't believe pathogens are responsible, so what factors do you think cause disease?

 

When you look into it, there is actually only a very limited set of factors external to the body that could cause disease. These factors include:

 

Environmental toxins, both manmade and natural

Radiations of various kinds, both manmade and natural

Medical drugs with adverse effects

Genetic factors

Epigenetic factors

Conditions during gestation 

Infectious pathogens (viruses, bacteria, fungi, parasites and archaea)

Diet and lifestyle factors

 

So if you are ruling out pathogens from disease aetiology, which of these other listed factors do you think precipitate disease?

 

Toxins? Well certainly there are a lot more of these in the environment since the Industrial Revolution; but people were still getting ill before industrialisation. 

I'm sorry, but I don't see the connection between type 1 diabetes and the current discussion here.

 

Of course, diseases are caused by pathogens, which is why we refer to them as such. The only question here is whether pathogens are the primary cause of age-related illnesses.

 

Regarding atherosclerosis, I think it's important to have a clear theory about how a virus can cause it before we consider these papers as evidence. Since macrophages are involved in the development of atherosclerosis, I expect many types of pathogens to be present in the plaque.

 

If pathogens really played a major role in age-related diseases, we would see these diseases much more often in young individuals. I mean, if all it really takes to catch a virus to get a heart attack, infants with untrained immune systems probably would be at high risk. I find this theory highly implausible.

 

Of course, pathogens can contribute to age-related deaths, but they are rarely the primary cause. COVID serves as a good example - most COVID-related deaths occurred in individuals who were already experiencing age-related declines in health. Thus these individuals did not really die because of SARS-Cov2 but because of aging. In fact, if we had a cure for aging, many of these people would still be alive today.

 

Therefore, while pathogens may play a role, the real issue lies in the natural weakening of the immune system as we age. This is the reason why elderly individuals may harbor various types of pathogens, but this does not necessarily mean that the pathogens are the primary cause of their health issues.

[Hip]

I'm sorry, but I don't see the connection between type 1 diabetes and the current discussion here.

 
Why, because you are just focusing on the diseases of ageing? Well you find that type 2 diabetes is also linked to various pathogens:

https://pubmed.ncbi....h.gov/16108236/
https://pubmed.ncbi....h.gov/19266182/
https://pubmed.ncbi....h.gov/19780970/


 

Regarding atherosclerosis, I think it's important to have a clear theory about how a virus can cause it before we consider these papers as evidence. Since macrophages are involved in the development of atherosclerosis, I expect many types of pathogens to be present in the plaque.

 

The way in which viruses and bacteria can induce cellular, tissue and organ dysfunction are many and varied. We may not yet know the particular mechanism for a given disease, because it takes a lot of work to figure out the mechanism; but finding pathogens in the diseased tissue is a red flag which promotes further investigation, to see if these pathogens might play a causal role in the disease. 

 

Pathogens can trigger disease because of harmful proteins and toxins they synthesise while living in the host. They can cause disease because of the collateral damage done by the immune system as it constantly tries to eradicate the pathogen. The can cause disease indirectly, by triggering autoimmunity (in this case, the location of the pathogen in the body may be different to the location of the disease, as autoimmunity once triggered can attack anywhere in the body).

 

Once classic example of an autoimmune disease triggered by a pathogen is Streptococcus sore throat triggered OCD or PANDAS. You get a sore throat from this bacterium, and because proteins on the bacterium are similar to proteins in the brain, the immune system mistakes these brain proteins for the bacterium, and attacks the brain. This constant immune attack of the brain leads to OCD. I believe about 25% of OCD cases have this Streptococcus origin.

 

 

 

If pathogens really played a major role in age-related diseases, we would see these diseases much more often in young individuals. I mean, if all it really takes to catch a virus to get a heart attack, infants with untrained immune systems probably would be at high risk. I find this theory highly implausible.

 
This is a good point to bring up, but I think we easily explain why pathogen-associated chronic diseases tend to appear later in life. For one thing, the immune system of children is stronger and more robust. Children generally have milder versions of a viral infection, compared to when adults catch the same infection.  For example, chickenpox in kids is mild, but can cause serious issues in adults.  

 

So children may be able to wipe out or control an infection before it gets a chance to disseminate into critical organs. For example, certain neurological diseases like Parkinson's are linked an enterovirus infection of brain cells. Now, in order to infect those brain cells, the virus first has to break into the brain. But if during the acute infection the virus is rapidly brought under control by a robust immune response, then that may prevent the virus ever reaching the brain. So a healthy immune response during the acute infection may help protect against chronic disease.

 

This may also explain why chronic stress has been linked to some diseases, as such stress is known to weaken Th1 antiviral immunity (though chronic stress actually boosts Th2 antibacterial immunity). If you were unlucky enough to catch a viral infection during a period of chronic stress, that virus would tend to run riot in your body, because of your weak immunity. This may then give the virus a chance to insinuate itself into critical organs like the brain, heart, etc, which may later precipitate a chronic disease. 

 

The other thing is that it is important to appreciate is that chronic diseases manifest slowly. Multiple sclerosis is strongly linked to EBV, and most people catch EBV in their teens or 20s, often from kissing. By 25 years old, about 90% of adults will have caught EBV. But you may only get MS when you are 40. So it may have taken a decade or two of having this virus in your body for it to precipitate the disease. 

 

So there can be decades of time lag between catching the pathogen, and the appearance of the disease. You can think of pathogen-caused chronic diseases as a very slow infectious disease, taken decades to manifest. This is another reason why chronic diseases will tend to appear later in life. 

Edited by Hip, 12 June 2023 - 09:00 PM.