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What Actually Causes Chronic Disease?

chronic disease etiology pathogens viruses bacteria

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#1 Hip

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Posted 12 May 2021 - 04:30 AM


Most age-related conditions/illness in the U.S. are lifestyle related. 

 

That lifestyle theory of disease is about as improbable as the four humors theory of illness that physicians promoted in Medieval times (where illness was considered to be caused by an imbalance between the four humors of phlegm, blood, yellow bile and black bile). 

 

The lifestyle theory is good if you just want a simplistic explanation that requires little understanding of biology. And it is good if you want to blame individuals for their own health woes.

 

Whereas the smart money is on infectious pathogens being the real causal factor behind most chronic disease. The body is an incredible machine which does not usually go wrong — unless there is some external factor introduced into it which throws a spanner in the works. That external factor may be a pathogen or a toxin. Most pathogens you catch during you life insinuate themselves permanently into your organs and tissues, where they live in a parasitic manner, slowly causing organ damage.

 

For example, when you look at heart valve disease, you find the diseased valves are infected with certain viruses.

 

No doubt exercise can be helpful for those with heart disease; but the underlying disease is not due to lack of exercise.


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#2 pamojja

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Posted 12 May 2021 - 12:49 PM

The lifestyle theory is good if you just want a simplistic explanation that requires little understanding of biology.


Lifestyle includes so much more than avoiding toxins. But also requires so much more common sense and dedication than the pharmacological-deficiency model.
 

And it is good if you want to blame individuals for their own health woes.


So you would use that theory exclusively to blame? Just as with religion? Which is often abused that way, without the inteligence to apply it to one's own life? - Your world-view seems to dictates that anyone not your view is stupid? - not recognizing the apparent lack of intelligence in such silly assumptions of yourself?


Had a walking disabilty from PAD. COPD stage1. ME/CFS symptoms.

The pharmaceutical-deficiency model only would have had a 1 in a 100 chance of reducing 5-year mortality. Nothing about remissions.

The life-style theory applied, did cause remission of all 3 conditions.
 


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#3 Hip

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Posted 12 May 2021 - 01:18 PM

Lifestyle includes so much more than avoiding toxins. But also requires so much more common sense and dedication than the pharmacological-deficiency model.

 
With your phobia of pharmaceuticals, everything you read seems to colored by that fear. 

 

The theory that most chronic diseases are caused by the pathogens we know are living our body tissues has nothing to do with the pharmaceutical industry. And indeed, it is unlikely that current chemical pharmaceuticals will ever be able to purge our bodies of these infectious pathogens, as pharmaceuticals (as well as herbs and supplements) are too blunt a tool. 

 

Antibiotics for example have been quite effective at quelling severe acute bacterial infections, and saving many lives as a result. But no antibiotic is able to fully purge a bacterium from the body entirely. That bacterium will always find nooks and crannies in the body to hide in, often actually within human cells (where it is more protected against immune attack and from antibiotics). So even after antibiotics, these bacteria remain at low levels in the body tissues, where they may trigger chronic disease.

 

Likewise with antivirals: most cannot fully eliminate a virus, they can only bring a severe acute infection under control. But most antiviral drugs cannot fully eliminate all traces of the virus from the body. So the virus remains hidden in certain tissues or organs, where it may cause a chronic disease.

 

I expect we will only have the medical technology to purge these pathogens once we start developing highly sophisticated biological interventions, like for example designer immune cells which can be injected into the body to intelligently kill infected cells and cancers. We need to better understand and harness biology in order to tackle chronic diseases and pathogens.

 

 

I think it is excellent when people do make lifestyle changes to help prevent or help ameliorate chronic disease. It shows virtue and a positive attitude. They are taking a positive approach in trying minimize the risk of disease. But even professional athletes get cancer and are hit with chronic disease. Exercise and healthy eating are no guarantee of immunity from chronic disease. 

 


Edited by Hip, 12 May 2021 - 01:21 PM.

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#4 Hip

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Posted 12 May 2021 - 01:33 PM

If anyone wants references for the fact that chronic low-level viral infection is found in the heart valve tissues in heart valve disease, see this study and this one

 

The general prevalence of valvular heart disease is around 2.5%. But it is more common in older people, so in the over 70s, 10% have it. Thus quite a few people may have these ongoing viral infections in their heart valve tissues.

 

 

If anyone has any other chronic disease they are interested in, let me know, and I should be able to find studies showing how that disease is linked to chronic low-level "smoldering" viral infection or bacterial infection. In almost every chronic disease you can think of, pathogens have been found lurking in the diseased tissues.


Edited by Hip, 12 May 2021 - 01:35 PM.

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#5 pamojja

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Posted 12 May 2021 - 02:03 PM

With your phobia of pharmaceuticals, everything you read seems to colored by that fear.

 
Only that ..I don't have fear of phamaceuticals. Because I informedly dissented. :laugh:

 

On the contrary: colored by the joy of remissions!
 

Exercise and healthy eating are no guarantee of immunity from chronic disease.

 
Again, lifestyle changes can include much more than that. In my case exercise only really played a role after the remission from the walking-disabilty.
 
For example, being born with pneumonia caused terrible toddler health for me, so much that I was spared the mumps and measles vaccines by responsible docs. Got them both as childhood-diseases instead, and therefore now enjoy life-long immunity. Just found out that measles and mumps experienced as a child reduces even the risks of certain cancers.
 
But to what this different approach really boil down to is well expressed in the expression: "the pathogen is nothing; the terrain is everything."
 
Though with 7 malarias, schistosomiasis, tuberculosis (despite vaccination) - all overcome - I would rather say "the pathogen takes everything, if the terrain is rooted out".
 
Remissions in my case wouldn't have been possible without carefully gardening the terrain.
 

..like for example designer immune cells which can be injected into the body to intelligently kill infected cells and cancers

 

Duh, didn't had time for that. Would since long be death. But to prop those 'designer' immune cells we already would have - if we didn't destroyed them with life-style choices - is something everyone can attempt to try now.


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#6 pamojja

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Posted 12 May 2021 - 02:09 PM

If anyone has any other chronic disease they are interested in, let me know, and I should be able to find studies showing how that disease is linked to chronic low-level "smoldering" viral infection or bacterial infection. In almost every chronic disease you can think of, pathogens have been found lurking in the diseased tissues.

 

Your thinking about smoldering pathogens seems to be in line with Dr. Levy's: https://rvr.medfoxpub.com/ - though you probably wouldn't agree with his solution.

 

In my case remission was possible only partially by adressing smoldering pathogens, by extracting a root-canal treated tooth.

 

 



#7 Hip

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Posted 12 May 2021 - 04:07 PM

But to what this different approach really boil down to is well expressed in the expression: "the pathogen is nothing; the terrain is everything."

 

That's a hackneyed phrase used a lot in alternative medicine circles; ironically I have noticed that people who use it tend to know little about either pathogens or the terrain in which they operate.

 

 

Yes, the host response to a pathogen is part of the picture (the "host response" or "host factors" are the terms scientists use for "terrain"). And drugs or supplements which modulate the host response can help fight pathogens. 

 

But nobody has yet been able to cure any pathogen-associated chronic disease, neither by targeting the pathogen with antimicrobials, nor by altering the host response — what you like to call the terrain. 

 

When humanity faces such enormously difficult problems like the issue of chronic disease, the intelligent person shows humility, and will admit that the problem is an extremely hard one. This is not a problem we will solve in one generation; it will take hundreds if not thousands of years. So you have to take a long-term view. 

 

 

 

The trouble with alternative medicine aficionados is their excessive conceit and hubris: they think they can cure anything with a few herbs, which is just laughable. Such excessive hubris is even frowned upon by religions. 

 

I will admit that when I was younger, I also had this hubris regarding health: I was foolish enough to think that by an ultra-healthy lifestyle I could avoid the major chronic diseases that plague humanity. Well then at the age of 40 I was hit with one of the worse illnesses you can get: myalgic encephalomyelitis (chronic fatigue syndrome) after catching an enterovirus. Only then did I realize that I had been rather naive in thinking that by virtuous healthy living I could sidestep all disease.

 

Sometimes I like to think that maybe my disease is here to teach me a lesson, to educate me, and make me less foolish regarding the actual causes of ill health. Although getting ME/CFS is a high price to pay for such an education.

 

I just wish I could get others to understand the perspective I have finally understood.


Edited by Hip, 12 May 2021 - 04:24 PM.

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#8 Hip

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Posted 12 May 2021 - 06:40 PM

The point I am making is that once you are hit with a chronic disease triggered by a virus, and once you start reading into medical science and realize so many chronic diseases are linked to infectious pathogens, you begin to understand where the real problem lies, in terms of what causes ill health.

 

You then become acutely aware of what humanity must do, if humanity ever is to aspire to living in a disease-free world: it must tackle the problem of disease-causing pathogens head on, using advances in science to do so. This is the education and understanding I have obtained from being hit with a virally-triggered disease.

 

Very few other people have realized that pathogens are most likely the root cause of chronic disease. Many people develop chronic diseases without any awareness that a pathogen may be the cause. And until people do realize this, and until humanity acts upon this knowledge, the human race will never be free from the affliction of disease.

 

 


Edited by Hip, 12 May 2021 - 06:42 PM.

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#9 pamojja

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Posted 12 May 2021 - 08:55 PM

Very few other people have realized that pathogens are most likely the root cause of chronic disease.

 

Is it?

 

Or rather as in the example of me entering this world soon after with pneumonia: wasn't it a rush Monday morning after a crazy full-moon night at that obstetric ward? My mother begging the stressed nurse repeatedly due to me choking to take care that any amniotic fluid still be removed? - The rest is history.

 

Was the pathogen, or simply circumstances the root cause of my pneumonia at birth?

 

If pathogens would be root-cause in chronic diseases, why I could get 3 of them into remission by addressing epigenetic factors only?

 

Why does it need in more than 90% an average of more than 2 other chronic diseases to make covid deathly?

 

https://www.scienced...3X16302403#bib4

Introduction

Asymptomatic, chronic viral infections occur in a large portion of humanity. It has been estimated that on average every human being can be concurrently infected with 8–12 chronic viral infections, caused either by DNA or RNA viruses [1]. Viruses considered to be commensal and opportunistic pathogens are widespread, especially in adults, and include members of the herpesvirus, adenovirus, papillomavirus, anellovirus, polyomavirus and circovirus families [2], [3]. Conversely, viruses associated with high morbidity and mortality such as hepatitis C virus, hepatitis B virus and human immunodeficiency virus (HIV) chronically infect millions of individuals [4].

 

Until a few years ago, the approaches applied to studying host immunity and viral virulence were mainly based on the analysis of symptomatic acute infections, and evaluated virus shedding and serological evidence of infection, together with the analysis of the immune responses of the host. Studies of acute infections have been relevant for analysing viral virulence and host immunity; however, the mechanisms that establish and perpetuate chronic viral infections are still not well known [1]. These mechanisms can be analysed taking into account the behaviour of a component of the microbiome, the virome. The microbiome, defined as all the microorganisms (viruses, bacteria, parasites and fungi) living within a human host, is a component of human physiology [5], while the virome is part of the microbiome of healthy humans, and includes the viruses (pathogenic and non-pathogenic) that infect the eukaryotic cells of the host, those that replicate in bacteria (bacteriophages or phages) and the endogenous viral elements [6]. A new and emerging concept includes the view that viruses may have deleterious or beneficial immunomodulatory effects other than affecting the adaptive and innate immune response [7], [8].

 

So up to 8-12 chronic viral infections on average in healthy persons with beneficial health effects too.

 

How could you still generalize pathogens as the root-cause of chronic disease? Co-evolution with pathogens might well be the reason humans have so successfully overtaken. We also own them most of our genes.

 

Conclusions

 

The asymptomatic chronic viral infections are part of the virome, that includes diseases and physiological effects. In particular, chronic herpesvirus infections are multifactorial infections arising from complex interactions among the herpesviruses, host factors, co-infections and other unknown aspects. Given the fact that the combinations of host, microbe and environment can happen in any host–microbe interaction, it has been proposed to dynamically adapt Koch's postulates adding the new findings on host–microbe relationship and microbial interactions [12], [60].

 

You can't simplify it to the point where you take the host, other commensal microbiomes or epigenetic influences and relations out of the equation. That is, if you really want to experience remission, and not only dream about an utopian world free of disease and suffering. Or beliefing that convincing others of your pet-theory would redirect resources to its solution. See the endless and profitable wars against cancer and CVD.

 

 

 


Edited by pamojja, 12 May 2021 - 08:58 PM.

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#10 Hip

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Posted 12 May 2021 - 09:43 PM

If pathogens would be root-cause in chronic diseases, why I could get 3 of them into remission by addressing epigenetic factors only?

 

Science does not even have much ability to control epigenetic factors at present, so your story of curing 3 diseases "by addressing epigenetic factors" sounds highly dubious to start with. Given the number of quacks and junk science articles you link to in your posts, I see your own story as likely just as bogus (be aware that if you quote quacks, it reflects on your own reputation).
 
 

 

How could you still generalize pathogens as the root-cause of chronic disease? Co-evolution with pathogens might well be the reason humans have so successfully overtaken. We also own them most of our genes.


If you are interested in the subject, you may like to read the works of Paul Ewald, who has proposed that pathogens will likely turn out to be the cause of most chronic diseases of currently unknown etiology. He has a book called Plague Time: The New Germ Theory of Disease, which I read. 

 

Ewald is not the only one who has proposed that pathogens are the likely root cause of chronic disease. There are also people like Hanan Polansky: see his book: Microcompetition with Foreign DNA and the Origin of Chronic Disease

 

But these really are difficult subjects for scientists to tackle, not the anti-science, anti-pharmaceutical and anti-vaccine hippies or anarchists among us who have quaint beliefs in Mother Nature. 

 


Edited by Hip, 12 May 2021 - 10:28 PM.

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#11 Hip

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Posted 12 May 2021 - 10:18 PM

 
The views of Gentile and Micozzi detailed in your above quote (copied below) are typical of the current medical profession and medical science, who tend to view pathogens in a rather black and white manner: either they immediately cause overt infectious disease (like HIV or hepatitis C virus do), or if they do not, then they are (incorrectly) considered perfectly benign. 
 
Well this is a foolish assumption, albeit a common one. 
 
Just because a virus does not immediately cause an infectious disease, this does not mean the virus cannot slowly and insidiously cause a chronic disease later (sometimes decades later).
 
It is known for example that Epstein-Barr virus (which most people acquire when they are in their teens or 20s) can sit in the body for decades, before it causes a cancer called nasopharyngeal carcinoma
 
There is no dispute at all that EBV causes this cancer, and no dispute at all that this cancer sometimes only appears decades after catching EBV. Google it if you want more info.
 
Likewise for the human papillomavirus, a cause of mouth cancer, which men can acquire from giving oral sex to women: this virus can sit in your body for years or decades before it triggers mouth cancer. The actor Michael Douglas believes his mouth cancer was due to all the oral sex he gave to hundreds of different women, during his sex-addicted life. Google it if you want more info.
 
So the black and white views of Gentile and Micozzi are at odds with the facts. Many viruses considered benign by some medics may be ticking time bombs which can later explode into cancer or chronic disease.
 

 

 

Viruses considered to be commensal and opportunistic pathogens are widespread, especially in adults, and include members of the herpesvirus, adenovirus, papillomavirus, anellovirus, polyomavirus and circovirus families [2], [3]. Conversely, viruses associated with high morbidity and mortality such as hepatitis C virus, hepatitis B virus and human immunodeficiency virus (HIV) chronically infect millions of individuals [4].

 

Source: here.

 
 

Edited by Hip, 12 May 2021 - 10:31 PM.

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#12 Florin

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Posted 13 May 2021 - 12:18 AM

That lifestyle theory of disease is about as improbable as the four humors theory of illness that physicians promoted in Medieval times (where illness was considered to be caused by an imbalance between the four humors of phlegm, blood, yellow bile and black bile). 

 

The lifestyle theory is good if you just want a simplistic explanation that requires little understanding of biology. And it is good if you want to blame individuals for their own health woes.

 

Whereas the smart money is on infectious pathogens being the real causal factor behind most chronic disease. The body is an incredible machine which does not usually go wrong — unless there is some external factor introduced into it which throws a spanner in the works. That external factor may be a pathogen or a toxin. Most pathogens you catch during you life insinuate themselves permanently into your organs and tissues, where they live in a parasitic manner, slowly causing organ damage.

 

For example, when you look at heart valve disease, you find the diseased valves are infected with certain viruses.

 

No doubt exercise can be helpful for those with heart disease; but the underlying disease is not due to lack of exercise.

 

This is kind of OT, but if the claim is that chronic disease could be wiped out if extrinsic causes of aging like lifestyle and pathogens were eliminated, that's obviously false. Otherwise, CRed, germfree mice would live forever, but they don't.

 

https://pubmed.ncbi....ih.gov/1748169/


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#13 Hip

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Posted 13 May 2021 - 01:31 AM

This is kind of OT, but if the claim is that chronic disease could be wiped out if extrinsic causes of aging like lifestyle and pathogens were eliminated, that's obviously false. Otherwise, CRed, germfree mice would live forever, but they don't.

 

https://pubmed.ncbi....ih.gov/1748169/

 

Nobody is saying that being germ-free will make you live forever. People will eventually die of old age, and I have no problem with dying of old age. But that's different to dying prematurely from a chronic disease, and having to suffer that chronic disease for decades while it is slowly killing you, and making you feel awful during the prime years of your life. 

 

Incidentally, so-called germ-free mice are not guaranteed germ free; they are only germ free with respect to our current ability to detect pathogens. But there are many pathogens we find very hard to detect, so the chances are that germ-free mice will harbor some viruses and other microbes.

 

The germ-free mice experiments are interesting, though.


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#14 Florin

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Posted 13 May 2021 - 02:46 AM

Nobody is saying that being germ-free will make you live forever. People will eventually die of old age, and I have no problem with dying of old age. But that's different to dying prematurely from a chronic disease, and having to suffer that chronic disease for decades while it is slowly killing you, and making you feel awful during the prime years of your life. 

 

The only big extrinsic factor that usually makes someone feel awful in middle age is morbid obesity, not germs (because germfree mice). In old age, chronic disease is caused mostly by intrinsic aging and the rest by lifestyle. So, even if you had a perfect lifestyle and avoided most of the morbidity of CVD and diabetes, you'd still eventually suffer a slow, nasty death from chronic diseases such as dementia and heart failure. Chronic disease is an inevitable consequence of the intrinsic causes of aging.

 

Incidentally, so-called germ-free mice are not guaranteed germ free; they are only germ free with respect to our current ability to detect pathogens. But there are many pathogens we find very hard to detect, so the chances are that germ-free mice will harbor some viruses and other microbes.

 

Our ability to detect pathogens seem good enough to conclude that germfree mice are really germ-free.

 

But if the germs you're talking about are impossible to detect, they are as relevant as any other invisible, impossible-to-detect entities.


Edited by Florin, 13 May 2021 - 02:49 AM.

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#15 Hip

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Posted 13 May 2021 - 12:48 PM

The only big extrinsic factor that usually makes someone feel awful in middle age is morbid obesity, not germs (because germfree mice). 


Obesity is also linked to viral infection: experimentally infect mice with adenovirus 36, and they rapidly become obese. This virus chronically infects the fat cells of mice (adipocytes), and causes these cells to malfunction and accumulate fat. 
 
In humans, 30% of obese people, but only in 11% of non-obese people are infected with adenovirus 36. Thus some researchers have proposed that the global obesity epidemic which began in the 1980s may in part be due to adenovirus 36. References: here, here, here and here

 

 

Metabolic syndrome, incidentally, is also linked to several pathogens, including Chlamydia pneumoniae, a bacterium which actually lives inside human cells (most bacteria live outside of cells, but some like CP live inside, where they are more protected from the immune system and from antibiotics). Metabolic syndrome is also linked to cytomegalovirus, and a few other pathogens. Reference: here.

 

 
 

In old age, chronic disease is caused mostly by intrinsic aging and the rest by lifestyle. So, even if you had a perfect lifestyle and avoided most of the morbidity of CVD and diabetes, you'd still eventually suffer a slow, nasty death from chronic diseases such as dementia and heart failure. Chronic disease is an inevitable consequence of the intrinsic causes of aging.

 
It is a common assumption that chronic disease is caused by aging itself, but like many common assumptions, may turn out to be incorrect. 

 

Very few people are aware of the pathogen model of chronic disease, and so they start making assumptions like this. 

 

But science is based on cause and effect. Each chronic disease has very specific characteristics, and thus there must be a very specific cause for that disease. The general "wear and tear" aging model would struggle to account for these highly specific characteristics that are present in diseases. Whereas pathogens in theory can easily account for them, as pathogens can be very specific regarding the organs, tissues and cell types they infect. Pathogens may also trigger autoimmune responses which again target very specific tissues or cellular receptors.

 

 

By the way, Alzheimer's has been linked to herpes simplex virus invasion of the brain. People with the APOE-4 genetic mutation are susceptible to having this virus break into the brain compartment, and cause a widespread slow infection of the brain. Ref: here

 

 

 

Our ability to detect pathogens seem good enough to conclude that germfree mice are really germ-free.
 
But if the germs you're talking about are impossible to detect, they are as relevant as any other invisible, impossible-to-detect entities.

 

Pathogen detection techniques are improving all the time, and made a big leap forward in recent years since the advent of massively parallel sequencing (also called high-throughput sequencing).

 

But unfortunately even with high-throughput sequencing, it is often impossible to detect pathogens unless you have an actual tissue sample (biopsy) from the relevant infected organ. It is not always possible to detect pathogens using blood samples, if the infection is localized in a particular organ. Some organs like the brain, the retina, etc are almost impossible to biopsy in living humans or animals. 

 

 

 


Edited by Hip, 13 May 2021 - 12:52 PM.

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#16 Florin

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Posted 13 May 2021 - 08:40 PM

Obesity is also linked to viral infection: experimentally infect mice with adenovirus 36, and they rapidly become obese. This virus chronically infects the fat cells of mice (adipocytes), and causes these cells to malfunction and accumulate fat. 
 
In humans, 30% of obese people, but only in 11% of non-obese people are infected with adenovirus 36. Thus some researchers have proposed that the global obesity epidemic which began in the 1980s may in part be due to adenovirus 36. References: here, here, here and here
 
 
Metabolic syndrome, incidentally, is also linked to several pathogens, including Chlamydia pneumoniae, a bacterium which actually lives inside human cells (most bacteria live outside of cells, but some like CP live inside, where they are more protected from the immune system and from antibiotics). Metabolic syndrome is also linked to cytomegalovirus, and a few other pathogens. Reference: here.


30% is still a minority, and I'm sure that even those people could shape up if they reduced their calorie intake enough.
 
Sure, pathogens may accelerate aging in some ways, but they're not the primary cause of aging. Most experts agree, and if you want to overturn this dogma, you need to generate (not find because it doesn't exist) a lot more evidence.
 

It is a common assumption that chronic disease is caused by aging itself, but like many common assumptions, may turn out to be incorrect. 
 
Very few people are aware of the pathogen model of chronic disease, and so they start making assumptions like this.


Again, most of the evidence seems to indicate that chronic disease cannot be avoided, because it is an inevitable consequence of intrinsic aging, regardless of the presence of pathogens. If you disagree, you'll need to do a lot of your own studies and experiments, because evidence for your position doesn't exist. Perhaps you can start by proving that germfree mice aren't really germfree.
 

But science is based on cause and effect. Each chronic disease has very specific characteristics, and thus there must be a very specific cause for that disease. The general "wear and tear" aging model would struggle to account for these highly specific characteristics that are present in diseases. Whereas pathogens in theory can easily account for them, as pathogens can be very specific regarding the organs, tissues and cell types they infect. Pathogens may also trigger autoimmune responses which again target very specific tissues or cellular receptors.

 

Pathogen theory struggles to account for the existence of germfree mice.
 

By the way, Alzheimer's has been linked to herpes simplex virus invasion of the brain. People with the APOE-4 genetic mutation are susceptible to having this virus break into the brain compartment, and cause a widespread slow infection of the brain. Ref: here

 

If you cure AD by getting rid of HSV, you'd just suffer from a non-pathogen caused dementia.
 

Pathogen detection techniques are improving all the time, and made a big leap forward in recent years since the advent of massively parallel sequencing (also called high-throughput sequencing).
 
But unfortunately even with high-throughput sequencing, it is often impossible to detect pathogens unless you have an actual tissue sample (biopsy) from the relevant infected organ. It is not always possible to detect pathogens using blood samples, if the infection is localized in a particular organ. Some organs like the brain, the retina, etc are almost impossible to biopsy in living humans or animals.

 

It's impossible-to-detect pathogens in germfree mice, but we know that these impossible-to-detect pathogens are present in germfree mice.


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#17 Hip

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Posted 14 May 2021 - 12:56 AM

30% is still a minority, and I'm sure that even those people could shape up if they reduced their calorie intake enough.

 
Reducing calorie intake to combat obesity does not cure the underlying disease of obesity: a healthy body automatically balances it weight without needing to drastically reduce calorie intake. In a healthy body, the amount of fat that adipocytes store is carefully controlled. In obesity, the adipocytes store too much fat.
 
So even if you manage to get your weight back to normal from caloric restriction, you still have the disease of obesity, because as soon as you return to the regular 2100 calories per day, you are going to put on weight again. The disease has not gone away, you are just controlling it using caloric restriction.

 

Whereas a health person does not put on weight eating the normal 2100 calories daily. 

 

It's like having diabetes, and controlling it using insulin. That works, but the underlying disease of diabetes has not gone away. 

 

 

 
 
30% is a minority, but there are likely other viral and possibly bacterial pathogens which may cause obesity. I had a slim athletic physique until I caught coxsackievirus B4. Then I put on 30 kg of weight, mostly around my abdomen (central obesity). Several friends who caught this virus from me also developed sudden central obesity.
 
The medical literature does not indicate any link between CVB4 and central obesity, but I was able to observe it in my "cohort".
 
 

 

Sure, pathogens may accelerate aging in some ways, but they're not the primary cause of aging. Most experts agree, and if you want to overturn this dogma, you need to generate (not find because it doesn't exist) a lot more evidence.

 
I am not suggesting pathogens are the primary cause of aging. Although chronic pathogens which increase body inflammation, generate reactive oxygen species and cause tissue degradation will likely accelerate aging, so I suspect certain pathogens may play a substantial role in aging. Here for example is a paper indicating that the nitrosative stress caused by nitric oxide (released by the immune system to fight pathogens) may be a substantial aging factor.
 
What I am saying is that researchers like Prof Paul Ewald and others believe pathogens, and the chronic diseases they may trigger, are the primary factors causing diminished healthspan and lifespan.
 
For practical longevity purposes, preventing diminshed healthspan and lifespan from chronic disease is far more important that preventing aging. 
 
Let's say for the sake of argument that tomorrow we discover a perfect drug which dramatically reduces aging, doubling human lifespan so that we can reach 200 years old. Well, few people will be able to take advantage of that increased lifespan, because at the moment, few people die of actual old age. Most at present die before they even get to 90, usually of some medical condition like a chronic disease or cancer. So it's clear that the major bottleneck in trying to live longer is not aging, but chronic disease and cancers.


 

Pathogen theory struggles to account for the existence of germfree mice.

 

I am not sure what you are getting at there. 

 

But on the subject of germ-free mice, I found this paper which says:

 

"Three viral agents have been detected so far in germfree mice, and these appear to be passed to their progeny by congenital route(s). All mouse strains carry leukaemia virus, some strains carry mammary tumour virus and one strain carries lymphocytic choriomeningitis (LCM) virus. Except for these, germfree mice are free of bacteria, fungi and parasites."

 

And that's just the viruses that have been detected so far in germfree mice. 

 

Another issue with using germfree mice is that because of the lack of a gut microbiome, these mice develop immune abnormalities. So they are not a very reliable model to investigate the effects of pathogens on health, especially since most chronic diseases involve the immune system.

 

Perhaps we really need to have mice which are free of pathogenic bacteria in their guts, but contain a healthy gut microbiome of friendly bacteria, so that they do not develop immune abnormalities. That would be a more sensible approach.

 

Even then, these mice will still habor some viruses.

 

 


Edited by Hip, 14 May 2021 - 01:29 AM.

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#18 Florin

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Posted 14 May 2021 - 05:57 AM

Whereas a health person does not put on weight eating the normal 2100 calories daily.
 
 
 
30% is a minority, but there are likely other viral and possibly bacterial pathogens which may cause obesity.


The other 70% of obesity isn't caused by pathogens. This is a fact, until it's proven otherwise. So, your claim about the weight of healthy people is not correct.
 

I am not suggesting pathogens are the primary cause of aging. Although chronic pathogens which increase body inflammation, generate reactive oxygen species and cause tissue degradation will likely accelerate aging, so I suspect certain pathogens may play a substantial role in aging. Here for example is a paper indicating that the nitrosative stress caused by nitric oxide (released by the immune system to fight pathogens) may be a substantial aging factor.
 
What I am saying is that researchers like Prof Paul Ewald and others believe pathogens, and the chronic diseases they may trigger, are the primary factors causing diminished healthspan and lifespan.
 
For practical longevity purposes, preventing diminshed healthspan and lifespan from chronic disease is far more important that preventing aging. 
 
Let's say for the sake of argument that tomorrow we discover a perfect drug which dramatically reduces aging, doubling human lifespan so that we can reach 200 years old. Well, few people will be able to take advantage of that increased lifespan, because at the moment, few people die of actual old age. Most at present die before they even get to 90, usually of some medical condition like a chronic disease or cancer. So it's clear that the major bottleneck in trying to live longer is not aging, but chronic disease and cancers.

 
You seem to believe that chronic diseases are different than "aging itself." This is a common misconception; in fact, there's no big distinction between aging and the diseases of aging.
 
https://www.youtube....tSUdOWVI&t=500s
 
Think about it like this: the only way that the aging process could kill is by causing chronic disease, and the reason the diseases of aging are "chronic" is that it usually takes a long time for damage to accumulate past the threshold that leads to death. The story about old people happily dying of "aging" in their sleep having escaped chronic diseases is a myth.
 
Most aging processes that create this accumulating damage in the body have nothing to do with pathogens. So, even if pathogens did not exist, you'd still die of chronic disease pretty much on schedule.

 

I am not sure what you are getting at there. 
 
But on the subject of germ-free mice, I found this paper which says:
 
"Three viral agents have been detected so far in germfree mice, and these appear to be passed to their progeny by congenital route(s). All mouse strains carry leukaemia virus, some strains carry mammary tumour virus and one strain carries lymphocytic choriomeningitis (LCM) virus. Except for these, germfree mice are free of bacteria, fungi and parasites."
 
And that's just the viruses that have been detected so far in germfree mice. 
 
Another issue with using germfree mice is that because of the lack of a gut microbiome, these mice develop immune abnormalities. So they are not a very reliable model to investigate the effects of pathogens on health, especially since most chronic diseases involve the immune system.
 
Perhaps we really need to have mice which are free of pathogenic bacteria in their guts, but contain a healthy gut microbiome of friendly bacteria, so that they do not develop immune abnormalities. That would be a more sensible approach.
 
Even then, these mice will still habor some viruses.


I'm getting at the fact that since the claim is that pathogens cause most or all chronic diseases, there would be no way for most chronic diseases to develop in germ-free mice by definition. But germ-free mice don't have superior health or longevity compared to gold standard CRed mice, so the claim that it's-all-about-the-pathogens can't be taken seriously.

 

That paper is outdated. Mice exist that are 100% germ-free.

 

https://www.taconic....-free-mice.html

 

In the absence of pathogens, the microbiome seems to just be about providing nutrients, but those nutrients can be added via artificial means. So, the microbiome should be an irrelevant variable in germ-free mice.



#19 Hip

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Posted 14 May 2021 - 02:42 PM

The other 70% of obesity isn't caused by pathogens. This is a fact, until it's proven otherwise. So, your claim about the weight of healthy people is not correct.

 
That statement is not a fact.

 

In science facts are things which are proven beyond doubt. Unless you actually prove that the other 70% of obesity cases are not caused by pathogens, then you cannot claim it is a fact.
 
Likewise, it is not a fact that the 30% of obese people with adenovirus 36 in their body have their obesity disease caused by this virus. Association does not mean causation. It is only a theory that adenovirus 36 causes obesity in humans. We know for a fact this virus causes obesity in mice however.
 
At present, we have hundreds of chronic diseases which are associated with pathogens, including obesity. But that association is not enough to prove that the pathogens cause those diseases. So at present, it is a theory or hypothesis that pathogens cause the chronic diseases they are associated with; further research is needed to prove (or disprove) this hypothesis.

 
 
 

You seem to believe that chronic diseases are different than "aging itself." This is a common misconception; in fact, there's no big distinction between aging and the diseases of aging.
 
https://www.youtube....tSUdOWVI&t=500s

 
I think it is possible to make a distinction between regular aging, and chronic disease-accelerated aging, although the distinction can be blurred.
 
Disease always involves an abnormal pathological mechanism: in disease there are pernicious process going on which do not occur in a non-diseased body. These pathological process can damage the body faster than normal aging. 
 
But even in a healthy non-diseased person, obviously there are processes on which cause aging. Just by breathing oxygen, we expose our bodies to damaging oxidative stress. But if you also have a disease which increases levels of reactive oxygen species and oxidative stress, that damage is accelerated.
 
 
 

 

I'm getting at the fact that since the claim is that pathogens cause most or all chronic diseases, there would be no way for most chronic diseases to develop in germ-free mice by definition. But germ-free mice don't have superior health or longevity compared to gold standard CRed mice, so the claim that it's-all-about-the-pathogens can't be taken seriously.
 
That paper is outdated. Mice exist that are 100% germ-free.
 
https://www.taconic....-free-mice.html
 
In the absence of pathogens, the microbiome seems to just be about providing nutrients, but those nutrients can be added via artificial means. So, the microbiome should be an irrelevant variable in germ-free mice.

 

It is a logical impossibility to prove that mice are germfree. It is always possible that some unknown virus exists in mice. New viruses are being discovered all the time.

 

Only recently was it proven that at least 33% of human have their breast tissues infected with bovine leukemia virus (BLV), a retrovirus in the same family as HIV. BLV is known to cause immune abnormalities in cows, but it is not yet known if it screws with the human immune system. But there is evidence BLV may trigger breast cancer.

 

Prior to this discovery of BLV in breast tissue, we had no idea that this virus existed in humans. We will likely find many more viruses hidden in the human body which we presently know nothing about. And the same applies to mice. 

 

So no way to prove that mice are free of exogenous pathogens.

 

 

 

And as mentioned, germfree mice have immune abnormalities because of the fact they don't have a gut microbiome. Their intestines are sterile.
 
Providing nutrients will not help, because the issue is the immune system not being "trained" and "configured" to operate normally by being naturally exposed to microbes in the gut. I quick Google search reveals that for example, Peyer's patches (an important gut immune organ) do not grow properly in germfree mice with no gut bacteria, and the gut lymph system does not mature properly either. 
 
 

Furthermore, all animals have viruses built-in to their genes, as part of their own DNA.
 
These built-in viruses are called endogenous retroviruses. An astounding 8% to 10% of the human genome is composed of human endogenous retroviruses (HERVs), and many of these HERVs have been linked to diseases. For example, the HERV-W family of endogenous retroviruses have been linked to multiple sclerosis. The mouse genome also contains 8% to 10% endogenous retroviruses.
 
No way to currently remove all these endogenous retroviruses in mice, because it would take an enormous amount of gene editing to remove them. And some endogenous retrovirus genes actually perform important functions in the animal, so not all endogenous retroviruses are pathogenic. So you would want to remove the pathogenic endogenous retroviruses, but not the beneficial ones, and that would be hard to judge.
 
 
If we are ever going to enjoy a golden era of human health, we will not only need to eliminate exogenous pathogens, but eventually we will need to edit our own genome to remove pathogenic HERVs. And of course remove gene mutations which are harmful, and there are plenty of those. One day I am sure humanity will do this. But we will need to learn much more about the functioning of these genes before we delete them, just in case they do perform some important role.
 
 
 
But in any case, can you show me any studies in which germfree mice have developed diseases which are linked to exogenous viruses, such as multiple sclerosis, type 1 diabetes, Alzheimer's, or heart valve disease? I could not find any when I looked just now. I don't mean mice which are genetically bred to develop certain diseases. I mean ordinary mice which were raised germ free. 

 

 


Edited by Hip, 14 May 2021 - 02:48 PM.

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#20 Florin

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Posted 15 May 2021 - 04:19 AM

That statement is not a fact.


Call it whatever you like: it's common knowledge that obesity can be eliminated in nearly anyone if calories are reduced regardless of the "real" cause of obesity.
 
But this only delays the inevitable; eventually, everyone will suffer from the same set of chronic diseases regardless of obesity or anything else.
 

I think it is possible to make a distinction between regular aging, and chronic disease-accelerated aging, although the distinction can be blurred.

 
You're probably thinking of the distinction between extrinsic (external causes of aging) and intrinsic (internal causes of aging that will still operate even if external causes are eliminated) aging. Obesity is mostly (ignoring genetic variation) an example of extrinsic aging and free radical creation via breathing is an example of intrinsic aging.
 
But again, even if extrinsic aging was eliminated somehow, intrinsic aging would produce the same set of chronic diseases shifted a few years into the future. Aging-related chronic diseases can be postponed but never avoided. This is due to the fact that both kinds of causes of aging produce the same kinds of damage in the body; eliminating extrinsic causes would slow the development of chronic diseases by only a small amount.
 

It is a logical impossibility to prove that mice are germfree. It is always possible that some unknown virus exists in mice. New viruses are being discovered all the time.
 
Only recently was it proven that at least 33% of human have their breast tissues infected with bovine leukemia virus (BLV), a retrovirus in the same family as HIV. BLV is known to cause immune abnormalities in cows, but it is not yet known if it screws with the human immune system. But there is evidence BLV may trigger breast cancer.
 
Prior to this discovery of BLV in breast tissue, we had no idea that this virus existed in humans. We will likely find many more viruses hidden in the human body which we presently know nothing about. And the same applies to mice. 
 
So no way to prove that mice are free of exogenous pathogens.

 
It seems far more likely that germ-free mice are 100% germ-free rather than not. These mice have probably undergone at least 100x more testing than any human tissue. So, the chance that even a single new pathogen will ever be found in these mice is so miniscule as to not be worth serious consideration.
 

And as mentioned, germfree mice have immune abnormalities because of the fact they don't have a gut microbiome. Their intestines are sterile.
 
Providing nutrients will not help, because the issue is the immune system not being "trained" and "configured" to operate normally by being naturally exposed to microbes in the gut. I quick Google search reveals that for example, Peyer's patches (an important gut immune organ) do not grow properly in germfree mice with no gut bacteria, and the gut lymph system does not mature properly either.


Germ-free mice can be customized with any microbiome you want.
 

Furthermore, all animals have viruses built-in to their genes, as part of their own DNA.
 
These built-in viruses are called endogenous retroviruses. An astounding 8% to 10% of the human genome is composed of human endogenous retroviruses (HERVs), and many of these HERVs have been linked to diseases. For example, the HERV-W family of endogenous retroviruses have been linked to multiple sclerosis. The mouse genome also contains 8% to 10% endogenous retroviruses.
 
No way to currently remove all these endogenous retroviruses in mice, because it would take an enormous amount of gene editing to remove them. And some endogenous retrovirus genes actually perform important functions in the animal, so not all endogenous retroviruses are pathogenic. So you would want to remove the pathogenic endogenous retroviruses, but not the beneficial ones, and that would be hard to judge.
 
 
If we are ever going to enjoy a golden era of human health, we will not only need to eliminate exogenous pathogens, but eventually we will need to edit our own genome to remove pathogenic HERVs. And of course remove gene mutations which are harmful, and there are plenty of those. One day I am sure humanity will do this. But we will need to learn much more about the functioning of these genes before we delete them, just in case they do perform some important role.


Yeah, but this retro stuff isn't really about pathogens; it's all about inherited genes, and that's intrinsic aging. Retros may contribute to the creation of senescent (or senescent-like) cells and nothing else as far as I know. The creation of these kinds of defective cells is inevitable, and regardless of what caused their creation, they'll be dealt with in the same way: by killing them off via senolytics or similar approaches.
 
So, again: the kinds of damage that accumulate due to intrinsic and extrinsic aging are the same and inevitably leads to the development of the same chronic diseases. The (SENS) solutions will also be the same.
 
https://www.sens.org...-jumping-genes/
 

But in any case, can you show me any studies in which germfree mice have developed diseases which are linked to exogenous viruses, such as multiple sclerosis, type 1 diabetes, Alzheimer's, or heart valve disease? I could not find any when I looked just now. I don't mean mice which are genetically bred to develop certain diseases. I mean ordinary mice which were raised germ free.


I don't know that much about chronic diseases in mice, but I do know that if the pathogen theory was correct, germ-free mice would be healthier and live longer than CRed, non-germ-free mice but that's not what happens.


Edited by Florin, 15 May 2021 - 04:30 AM.

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#21 Hip

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Posted 15 May 2021 - 02:56 PM

I don't know that much about chronic diseases in mice, but I do know that if the pathogen theory was correct, germ-free mice would be healthier and live longer than CRed, non-germ-free mice but that's not what happens.

 

Well, chronic disease is what I am talking about. If you wanted to disprove the pathogen theory of chronic disease, you would have to demonstrate that germ-free mice suffer the same chronic disease as mice exposed to germs which are linked to various chronic diseases. (And in this experiment you would have to use germ-free mice which in which a healthy microbiome was introduced into their guts at birth, otherwise these mice are going to develop immune abnormalities which would invalidate the experiment).

 

But if it turns out that only the mice exposed to pathogens develop the disease linked to those pathogens, then this would support the pathogen theory of chronic disease.

 

I do not think anyone has done this experiment.  

 

 

 

To do this experiment, you would need not only to have a group of germ-free mice (brought up with an added health gut microbiome), but you would also need various other groups of mice to compare to which were deliberately infected with the pathogens known to be linked to chronic disease.

 

You would have to deliberately infect the mice with these pathogens, otherwise they may not catch the right pathogens. Mice kept under clean lab conditions are likely not going to be placed in contact with the pathogens they would be exposed to in the wild. So you would have to deliberately expose them to the relevant viruses and bacteria.

 

I am not aware of anyone who has conducted such an experiment. 

 

 

 

Also, sometimes it requires a virus along with a second factor (such as certain genetics, or toxin exposure) before a mouse develops the chronic disease. For example, in a mouse model, Crohn's disease can be precipitated by a norovirus, but only when both a specific gene variant is present and a certain toxin has damaged the gut. Ref: here.


Edited by Hip, 15 May 2021 - 02:57 PM.

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#22 Florin

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Posted 15 May 2021 - 07:48 PM

I'd be very surprised if these experiments haven't been already performed either intentionally or unintentionally. As I pointed out before, germ-free mice with custom microbiomes are readily available but aren't significantly healthier (have less chronic disease) than non-germ-free mice. A lot of experiments have been performed with wild-type mice, and non-germ-free lab mice are often infected either intentionally or unintentionally with pathogens. If it's so hard to infect mice with the right pathogens as you seem to imply, that means pathogens are unlikely to be a significant cause of chronic diseases in mice. If the pathogen theory of chronic disease was correct, experiments with mice should have provided plenty of evidence in its favor by now.

 

But in the unlikely event that that the right experiments haven't been performed, this also means that the pathogen theory currently lacks evidence for its correctness. So why should we led it more credence than more established theories?

 

And as I mentioned before, the solutions for the elimination of chronic disease are the same regardless of the ultimate reasons that cause damage to accumulate in the body over time.



#23 Hip

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Posted 15 May 2021 - 10:55 PM

I'd be very surprised if these experiments haven't been already performed either intentionally or unintentionally. As I pointed out before, germ-free mice with custom microbiomes are readily available but aren't significantly healthier (have less chronic disease) than non-germ-free mice.

 
Would you have any studies that you can link to which demonstrates this? When I did a quick Google, I could not find any. 
 
 

 

If it's so hard to infect mice with the right pathogens as you seem to imply, that means pathogens are unlikely to be a significant cause of chronic diseases in mice. 


Mice and rats living in their natural environment out in fields and streams will likely be exposed to a lot more pathogens than mice living in clean plastic boxes in a lab. Being in a plastic box mice run is like living in lockdown conditions, because they are not in contact with any other mice or animals which might spread infections by animal-to-animal contact.

 

In a lab, mice may pick up some infection from the humans caring for them, but in many cases, mice have their own version of each virus, and the human version does not infect mice, and vice versa. Human cytomegalovirus does not properly infect mice, and mouse cytomegalovirus does not properly infect humans, for example.

 

 

 

But in the unlikely event that that the right experiments haven't been performed, this also means that the pathogen theory currently lacks evidence for its correctness. So why should we led it more credence than more established theories?

 

What established scientific theories of chronic disease are there? There are very few actually. And theories that were once considered viable have now been struck off the list of possibilities.

 

20 years ago, it was thought that genes would explain nearly all chronic diseases, if only we were able to fullly sequence the human genome.

 

This belief that genes would underpin almost every disease was the driving motivation to get the human genome sequenced, which was finally achieved in 2003, at the cost of around $2 billion in today's money. The sequencing of the human genome was considered so important for the advancement of medical science, that President Clinton actually announced when this massive international project was complete. 

 

But once we had all this genetic data to hand, it turned out that genes were not responsible for most chronic diseases. Which was a huge blow to the dreams of medical researchers, who wanted to understand the root cause of disease. Sure, genes may play a limited partial role in some diseases, and people with certain genes may be more predisposed to developing certain diseases; but that's about as far as it goes. We now know that genes are not the fundamental causal factor in most chronic disease (with a few notable exceptions like Huntington's disease, which is primarily genetic).

 

So we have to look for other fundamental causes of chronic diseases. And there are not many causes about: in terms of possible causes, you have only around 6 possible causes: genes, epigenetic factors, diet/lifestyle factors, conditions in the womb during gestation, environmental toxins (man-made and natural toxins, including radiation), and finally the pathogenic microorganisms living in a host.

 

That's all the causes that exist. Thus the causes of chronic disease must be found in that list. And we know we can cross out genetics, because that failed to provide the answers. And toxins are not that likely either, since chronic disease existed long before all the modern man-made chemical toxins we now find in our environment (though numerous studies show toxins do play a causal role in triggering chronic disease).

 

So when you do this detective work, and narrow it down to the feasible causal culprits, you see that there are very few culprits in the identity parade line up. And infectious pathogens, which are the oldest enemy of mankind, responsible for killing more humans than any other cause, is standing right there in the line up, with a murderous look on its face!

 

 

 


Edited by Hip, 15 May 2021 - 11:13 PM.

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#24 Hip

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Posted 15 May 2021 - 11:28 PM

This thread has been set up to discuss scientific theories on chronic disease and cancer causality. In other words, what are the causal factors which trigger a chronic disease or cancer?



#25 Florin

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Posted 16 May 2021 - 08:05 PM

Would you have any studies that you can link to which demonstrates this? When I did a quick Google, I could not find any.


I haven't looked at any study, but as I mentioned, I'd be surprised if those sorts of studies haven't been done. And since mice with custom microbiomes exist, the companies raising them (to sell to researchers) would almost certainly have noticed if these mice were significantly healthier than other mice.
 

Mice and rats living in their natural environment out in fields and streams will likely be exposed to a lot more pathogens than mice living in clean plastic boxes in a lab.


I've already pointed out that plenty of experiments with wild-type mice have been performed and nothing unusual has been found.
 

So we have to look for other fundamental causes of chronic diseases. And there are not many causes about: in terms of possible causes, you have only around 6 possible causes: genes, epigenetic factors, diet/lifestyle factors, conditions in the womb during gestation, environmental toxins (man-made and natural toxins, including radiation), and finally the pathogenic microorganisms living in a host.
 
That's all the causes that exist. Thus the causes of chronic disease must be found in that list. And we know we can cross out genetics, because that failed to provide the answers. And toxins are not that likely either, since chronic disease existed long before all the modern man-made chemical toxins we now find in our environment (though numerous studies show toxins do play a causal role in triggering chronic disease).


The most established theory in gerontology for the development of chronic diseases is the theory of the accumulation of stochastic (random) damage due to extrinsic and intrinsic aging. Except for perhaps epigenetics, the causes you mentioned are causes of extrinsic aging. The gene theory of chronic disease was never popular among gerontologists. And while the most significant extrinsic cause is known to be lifestyle, most gerontologists would probably agree that even if all extrinsic causes of aging were eliminated, the same types of damage will continue to accumulate due to intrinsic causes alone, and so, most chronic diseases won't be eliminated by definition. Intrinsic aging is caused by the normal operation of metabolism which has a lot of chaotic processes that generate damage all of the time, and so, intrinsic aging is impossible to eliminate. One way around this problem is to periodically repair this accumulating damage using SENS. Another framework is The Hallmarks of Aging, which is not so great in my opinion.
 
https://www.youtube....h?v=AvWtSUdOWVI
https://doi.org/10.1....2002.tb02115.x

https://dx.doi.org/1...ell.2013.05.039


Edited by Florin, 16 May 2021 - 08:06 PM.


#26 Hip

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Posted 16 May 2021 - 10:24 PM

I haven't looked at any study, but as I mentioned, I'd be surprised if those sorts of studies haven't been done.


To use a study to support an argument, it's no good saying "I have not seen any such studies, but I'd be surprised if those studies haven't been done". You really need to link to a study. And you need a study whose findings support your assertion.
 
I could not find any such studies when I Google searched. But I did find this Wikipedia article which says:
 
"Due to lacking a healthy microbiome, many germ-free organisms exhibit major health deficits."
"Germ-free mice have been shown to have defects in their immune system and energy uptake due to lacking a healthy microbiome."
"There is also strong evidence for interactions between the mouse microbiome and its brain development and health."
 
So the whole model of germ-free mice is unsuitable for testing the health effects of pathogens, because these mice have health issues to begin with, due to the lack of a gut microbiome.
 


 

I've already pointed out that plenty of experiments with wild-type mice have been performed and nothing unusual has been found.


Wild-type mice are not the same as mice living out in the wild. "Wild-type" just means taken from the wild, but not living in the wild.



 

The most established theory in gerontology for the development of chronic diseases is the theory of the accumulation of stochastic (random) damage due to extrinsic and intrinsic aging. Except for perhaps epigenetics, the causes you mentioned are causes of extrinsic aging. The gene theory of chronic disease was never popular among gerontologists. And while the most significant extrinsic cause is known to be lifestyle, most gerontologists would probably agree that even if all extrinsic causes of aging were eliminated, the same types of damage will continue to accumulate due to intrinsic causes alone, and so, most chronic diseases won't be eliminated by definition.

 

I agree it is likely the age-related build up of damage in the body will be a contributing factor to the risk of developing a chronic disease or cancer. 

 

But clearly age-related damage cannot be the fundamental cause of most chronic diseases and cancers, as you can be hit with these diseases at a young age, sometimes even before you have fully grown and have reached adulthood. 

 

Type 1 diabetes you can get when you are 5 years old. Heart valve disease can occur in children. Myalgic encephalomyelitis can hit in adolescence. Alzheimer's or Parkinson's can hit in your 30s. Cancer also hit in young children as well as adults. Etc, etc.

 

So age-related damage might increase the risk of developing a chronic disease. But this aging damage cannot be the fundamental mechanism of chronic disease, otherwise you would only see chronic diseases appearing in middle age or elderly adults. 

 

 

 

Age-related damage is not the only mechanism by which an older age puts you at higher risk for chronic disease: there is also the fact that the longer we live, the more pathogens we pick up, so that when you are 70, you will have more viral and bacterial pathogens living in your body compared to when you were 20. Most people at 20 do not have cytomegalovirus in their body. But most people at 70 do. Ref: here. That's just one example. Our total viral and pathogenic body load increases each year we live. 

 

Plus as you get older, due to aging, your immune system becomes less efficient at controlling and suppressing the infections that live in your body.

 

In the pathogen theory of chronic disease, the more pathogens inhabiting your body tissues and organs, the more likely you are to develop a chronic disease. So this is another factor which may explain why cancers and chronic diseases are more prevalent in older people compared to younger people.

 

 

 

If you want to see a great video by Prof Paul Ewald on the pathogen theory of cancer, see here: toward a unified, evolutionary theory of cancer

 

Remember that at present, all theories of chronic disease etiology are just that — theories. So whatever the current generation of gerontologists say or believe regarding disease causality, this is only their opinion or hypothesis. We are still waiting for the Einstein or Newton of medical science to come along and uncover the true causes of chronic disease. I would put my money on the pathogen theory turning out to be correct.

 

  

 


Edited by Hip, 16 May 2021 - 10:54 PM.


#27 Hip

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Posted 16 May 2021 - 10:50 PM

Here is a whole list of fascinating articles on the pathogen theory of chronic disease and cancer. Note that this pathogen theory applies both to physical diseases, as well as mental health illnesses (mental symptoms may be due to physical brain dysfunction). Lots of people suddenly develop mental health issues out of the blue, for no apparent explanation. A new pathogen which they caught some time earlier may be the explanation.

 

 

 

 

 

 

 

 


Edited by Hip, 16 May 2021 - 10:52 PM.

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#28 Florin

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Posted 18 May 2021 - 01:27 AM

So the whole model of germ-free mice is unsuitable for testing the health effects of pathogens, because these mice have health issues to begin with, due to the lack of a gut microbiome.

 
GF mice with custom microbiomes have recently become available and GF mice with ASF microbiomes have been around for decades.
 
https://www.globenew...e-Profiles.html
https://www.taconic....ic-rodents.html
 

Wild-type mice are not the same as mice living out in the wild. "Wild-type" just means taken from the wild, but not living in the wild.

 
Unless you have a good counter argument, I'm going to assume that they're similar enough.
 

I agree it is likely the age-related build up of damage in the body will be a contributing factor to the risk of developing a chronic disease or cancer. 
 
But clearly age-related damage cannot be the fundamental cause of most chronic diseases and cancers, as you can be hit with these diseases at a young age, sometimes even before you have fully grown and have reached adulthood. 
 
Type 1 diabetes you can get when you are 5 years old. Heart valve disease can occur in children. Myalgic encephalomyelitis can hit in adolescence. Alzheimer's or Parkinson's can hit in your 30s. Cancer also hit in young children as well as adults. Etc, etc.
 
So age-related damage might increase the risk of developing a chronic disease. But this aging damage cannot be the fundamental mechanism of chronic disease, otherwise you would only see chronic diseases appearing in middle age or elderly adults.

 
It all boils down to damage, because it would be physically impossible for the body to malfunction if it isn't damaged by definition.
 
Besides extrinsic factors, the causes of disease at a young age can be attributed to congenital factors (e.g., bad genes) or just being unlucky (e.g., winning to cancer mutation lottery earlier than usual).
 

Age-related damage is not the only mechanism by which an older age puts you at higher risk for chronic disease: there is also the fact that the longer we live, the more pathogens we pick up, so that when you are 70, you will have more viral and bacterial pathogens living in your body compared to when you were 20. Most people at 20 do not have cytomegalovirus in their body. But most people at 70 do. Ref: here. That's just one example. Our total viral and pathogenic body load increases each year we live. 
 
Plus as you get older, due to aging, your immune system becomes less efficient at controlling and suppressing the infections that live in your body.
 
In the pathogen theory of chronic disease, the more pathogens inhabiting your body tissues and organs, the more likely you are to develop a chronic disease. So this is another factor which may explain why cancers and chronic diseases are more prevalent in older people compared to younger people.

Remember that at present, all theories of chronic disease etiology are just that — theories. So whatever the current generation of gerontologists say or believe regarding disease causality, this is only their opinion or hypothesis. We are still waiting for the Einstein or Newton of medical science to come along and uncover the true causes of chronic disease. I would put my money on the pathogen theory turning out to be correct.

 

It doesn't matter: pathogens/lifestyle/programmed aging/metabolism/entropy/whatever -> damage -> pathology -> death


Edited by Florin, 18 May 2021 - 01:44 AM.


#29 Hip

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Posted 18 May 2021 - 01:56 AM

GF mice with custom microbiomes have recently become available and GF mice with ASF microbiomes have been around for decades.


OK, I does look like these mice are available. So it is now just a case of seeing if anyone has conducted chronic disease susceptibility studies on these germ-free mice with custom microbiomes.



 

Unless you have a good counter argument, I'm going to assume that they're similar enough.


If you take mice out of the wild, and breed them in the lab, they are classed as wild-type mice. But because they are not living in the wild, they will not be exposed to all the natural infections found in the wild.  



 

It all boils down to damage, because it would be physically impossible for the body to malfunction if it isn't damaged by definition.


Chronic diseases are divided into two types: structural diseases and functional diseases. In structural diseases, there is physical damage to be seen. Like in multiple sclerosis, the brain lesions caused by the autoimmune attack can be observed on MRI.

However, in functional diseases, no major structural damage can be found, and instead it is the functioning of the body which goes wrong. The disease I have, myalgic encephalomyelitis, is considered a functional disease, because very little structural damage can be found in ME/CFS. You can have terrible brain fog, yet the brain looks normal on MRI.

 

How might pathogens cause functional diseases? Well, once you have a pathogen living inside your cells, that pathogen introduces its own genes and proteins to the cell. Thus the cell is no longer a pure human cell, but has foreign genes living in it, and altering the functioning of the cell.

One of the most common activities of pathogens living in the body is immune disruption: pathogens are like computer hackers: they are able to hack the host immune system and cause it to malfunction. Pathogens do this for survival reasons, because by throwing a spanner into the workings of the immune system, pathogens living in your body avoid being destroyed by the immune system.

So now you have a situation where you immune system is not working properly, which might lead to chronic disease. Or perhaps a hacked immune system may allow a cancer to grow when that cancer would have normally been destroyed by the immune response.

 

 

 

Besides extrinsic factors, the causes of disease at a young age can be attributed to congenital factors (e.g., bad genes) or just being unlucky (e.g., winning to cancer mutation lottery earlier than usual).


I think we have already established that genes are not the long sought after causal factor behind most chronic diseases.

 

Thus we still need to find why a perfectly healthy child suddenly can develop type 1 diabetes.

 

Clue: if you examine the insulin-producing cells in T1D, you find that they are infected with coxsackievirus B4.
 


Edited by Hip, 18 May 2021 - 01:57 AM.


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#30 Florin

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Posted 19 May 2021 - 04:30 AM

OK, I does look like these mice are available. So it is now just a case of seeing if anyone has conducted chronic disease susceptibility studies on these germ-free mice with custom microbiomes.


If there was anything to the pathogen theory, it would have been noticed if these GF mice were healthier than CRed non-germ-free mice.
 

If you take mice out of the wild, and breed them in the lab, they are classed as wild-type mice. But because they are not living in the wild, they will not be exposed to all the natural infections found in the wild.

 
Some studies are performed on mice taken directly from the wild.
 
Mice that are bred in the lab might be reinfected by mice (like their mothers) that were captured in the wild.
 

Chronic diseases are divided into two types: structural diseases and functional diseases. In structural diseases, there is physical damage to be seen. Like in multiple sclerosis, the brain lesions caused by the autoimmune attack can be observed on MRI.

However, in functional diseases, no major structural damage can be found, and instead it is the functioning of the body which goes wrong. The disease I have, myalgic encephalomyelitis, is considered a functional disease, because very little structural damage can be found in ME/CFS. You can have terrible brain fog, yet the brain looks normal on MRI.


There's no such thing as a purely functional, chronic disease absent structural damage. This is physically impossible.
 
Chronic immune system dysfunction is mostly caused by:

  • anergic immune cells (due to shortened telomeres or inappropriate receptors)
  • thymus involution (due to cell loss)
  • lymph node fibrosis (probably due to senescent cells and other damage)
  • inappropriate response of healthy immune cells to damage elsewhere (destroying tissue due to senescent cell signaling or causing athero plaques to form due to getting overwhelmed by the intake of oxidized cholesterol).

This is all structural damage.

 

Detecting some of this damage can be tricky. For instance, senescent cells release SASP due to precancerous mutations and mutations in mitochondria make cells release free radicals that can cause healthy cells (include brain cells) to become "unhappy." None of this is easily detectable with any external device.
 
Factors not directly related to aging such as genetic variation may make some people more susceptible to this damage than others.
 

How might pathogens cause functional diseases? Well, once you have a pathogen living inside your cells, that pathogen introduces its own genes and proteins to the cell. Thus the cell is no longer a pure human cell, but has foreign genes living in it, and altering the functioning of the cell.

One of the most common activities of pathogens living in the body is immune disruption: pathogens are like computer hackers: they are able to hack the host immune system and cause it to malfunction. Pathogens do this for survival reasons, because by throwing a spanner into the workings of the immune system, pathogens living in your body avoid being destroyed by the immune system.

So now you have a situation where you immune system is not working properly, which might lead to chronic disease. Or perhaps a hacked immune system may allow a cancer to grow when that cancer would have normally been destroyed by the immune response.

 

That's damage to the structure of DNA which would most likely lead to cell senescence or cancer. The solution is the same: kill the senescent cell or prevent a tumor from growing too big (WILT or some other cancer cure-all).
 

I think we have already established that genes are not the long sought after causal factor behind most chronic diseases.


Genetic variation doesn't directly cause most chronic diseases, but it can allow damage to accumulate more quickly than otherwise would be the case.







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