De Grey responded, “Because I am an old man. I am 158.”

Aubrey de Grey

It has been three years since then and at the ripe age of 161 (according to his Wikipedia bio, his birthday is in April), Aubrey de Grey presided over the latest of the Methuselah Foundation’s annual anti-aging symposiums. At the end of June 2008, a group of us with ties to Autoimmunity Research Foundation attended that meeting on the *very* sunny campus of UCLA. Our goal was to get researchers thinking about a bacterial explanation for diseases of the aging, and to get them to begin considering the Marshall Protocol as an anti-aging option.

Aubrey de Grey is always surrounded by people, be they prestigious presenters, researchers, conference organizers, or any of his small army of energized volunteers for which he plays field marshall.

De Grey is an eminently likable guy. Although he talks in an impatient staccato, he seems to be an accomplished listener. You can tell he’s listening because he’s thoughtfully tugging on his beard, as if that were some lever that, when pulled, speeds up his thought process.

It’s hard to read too much into why a 45-year old (you knew he was joking about 158, right?) opts to sport a two-foot beard, but I’m pretty sure it may have something to do with the fact he has fully embraced his– some might say, quixotic– quest.

Those of us associated with the Marshall Protocol know what it’s like to be thought of as quixotic: “I can understand how the Marshall Protocol could treat a single indication or even disease, but dozens of them? There’s no way that could be true….” Yup, we hear that a lot.

De Grey’s engaging personality, enthusiasm, and scientific prowess have made him a singular catalyst for the anti-aging movement. It has also earned the man a sizable following from a group including scientists, doctors, entrepreneurs, drug manufacturers, and young students, all of whom share the belief that the end of aging is at hand and only requires the right mix of funding, technology, and an evolution in social attitudes towards aging. De Grey argues that aging is a disease and a curable one at that.

The first day of the Conference, I attended the press conference with a press pass for Bacteriality. During the sound check, I chatted with a group of graduate students who were filming a movie about aging.  As is my custom, I described Dr. Marshall’s work. When the full implications of the MP became clear to them, the grad students’ expressions peaked, and I arranged to do an interview about the MP for their movie (I have no idea when or where it might come out).

The open-mindedness we saw from the pair of filmmakers was largely consistent with what we saw from others. In my opinion, this perspective is a very sensible one. After all, right now, there are precious few curative therapies for any of the diseases of the aging.

Even at an anti-aging conference, the ARF’s work is unique because, as Dr. Marshall alluded to in his talk, the ARF is studying “living, breathing human subjects” rather than fruit flies, rats or even higher primates.

Lunchtime, which lasted for several hours, provided an excellent opportunity to speak with others present.  Lunch was served buffet style and tables were scattered on one of the campus greens in the open air.  About four tables were in the shade, and naturally those of us with Autoimmunity Research Foundation made an effort to grab the shady seats as quickly as possible.  Since it turned out that most other attendees also sought to avoid the California sun, extra chairs were pulled up to the shady tables and each became a hub of discussion that frequently focused on the Th1 pathogens or the immunosuppressive effects of vitamin D. 

It became abundantly clear that the doctors, scientists, and drug manufacturers present had, until speaking with myself or other members of ARF, simply failed to factor chronic bacteria into the aging process.  The same proved true when it came to the researchers giving official talks (Dr. Marshall aside of course!).  For example, on Saturday morning, Dr. Jerry Shay of University of Texas Southwestern Medical Center gave a talk that discussed DNA repair.  At the end of his presentation, I asked the following question:  “Chronic intracellular bacteria… could they be interfering with the processes of transcription, translation and, most importantly, DNA repair in the nuclei of cells?”  After a brief pause and a quick scratch of his head, he replied that he had simply not considered the possibility. 

Rather, most of the talks fit into the model of aging first invoked by de Grey at the inception of the Conference – a model in which the human body is thought of as a car.  Over the years, cars inevitably accumulate damage and generally end up at the repair shop and finally at the dump.  But, as de Grey made clear, much can be done to keep a vehicle in prime condition.  Periodic oil checks, trips to the mechanic for touch-ups before damage occurs, great care in terms of keeping the car clear of scratches and dents – all this can allow the vehicle to function for a much longer period of time.  In fact, if enough effort is invested into a vehicle, it might be able to run forever. 

The metaphor of the human body as a car suggests that all the “junk” (toxins, debris, waste products, etc.) that causes the tissues to age is created by the body itself.  Yet such a model, in my eyes, fails to take into account the severe symptoms caused by diseases of the aging or the extensiveness of the aging process itself.  Sure, the human body will experience wear and tear over time, but can the purely intrinsic accumulation of “junk” suffice to cause conditions as serious as Alzheimer’s disease or as deadly as cancer and cardiovascular disease? 

Isn’t it more logical that external/environmental factors are also driving these serious states of decline and that, based on the recent findings of biomedical researcher Trevor Marshall, chronic intraphagocytic bacteria are the most obvious culprits contributing to tissue degradation, decay, and biological waste products?

And sure enough, the talks given by other researchers frequently supported the Marshall Pathogenesis, even if the scientists presenting the data have yet to realize why.  The importance of maintaining an active innate immune response in order to defy aging was brought up on several occasions. 

Everyone seemed to agree that the full complement of diseases of the aging were connected to inflammation, a concept invoked numerous times by the Conference’s speakers. It was an exercise in self-restraint not to stand up in my seat and shout to the crowd, “Chronic inflammation is the result of chronic bacterial infection!!”

Chatting with fellow participants in front of my poster.

Take our telomeres – the DNA sequences at the ends of human chromosomes that get shorter with every cell division.  Eventually telomeres shorten to a point where a cell can no longer divide and the body loses its ability to effectively produce new cells.  Several of the speakers correlated numerous chronic inflammatory diseases with the presence of shorter telomeres, including not just cancer and Alzheimer’s but also illnesses like ulcerative colitis and idiopathic pulmonary fibrosis (clearly a Th1 disease!).   Since we know these diseases are caused by pathogens, it’s very likely that the shortened telomeres observed in patients with these conditions stem from the fact that chronic bacteria and viruses can mutate telomeric DNA, causing it to shorten at a faster rate. 

If telomeric DNA is mutated by the Th1 pathogens, then such knowledge can greatly aid scientists who are already working on procedures that would allow for the extension of telomere length (several of whom spoke at the Conference).  For example, in an excellent talk called, “The Struggle to Keep Our Telomeres Long,” Laura Briggs of the Sierra Sciences Research Group discussed a current conundrum faced by telomere researchers. 

Briggs and others have developed techniques that can potentially lengthen our telomeres, but they are faced with the dilemma that extending the lifespan of our healthy cells will also extend the lifespan of our cancer cells (and, I might add, infected cells). As Briggs stated, “This leaves us with the irrefutable conclusion that we will be unable to significantly extend our lifespans without finding a cure for cancer that doesn’t limit our ability to extend the lengths of our telomeres.” 

Well… what if I argued that killing the Th1 pathogens with the Marshall Protocol and maintaining the integrity of the VDR and the innate immune response is very likely the cure for cancer that Briggs seeks? One of Dr. Marshall’s talk’s most provocative points is that in a cohort of over 500 high-risk patients who have been followed for up to five years, there has been no incidence of metastasis. With such knowledge at hand, defying aging by successfully lengthening our telomeres is a much more plausible possibility.

Several talks also focused on what are referred to as “senescent” cells – cells that fail to undergo the usual process of cell death and instead enter a stable and essentially irreversible growth-arrest state.  Senescent cells have been shown to accumulate with age and with age-related diseases, making it clear that the presence of these cells contributes to the aging process and disease in general.   And while the reason behind the formation of senescent cells remains a mystery to the medical community at large, it’s quite probable, at least in my eyes, that senescent cells are simply infected cells.
 
As Judith Campisi of the Lawrence Berkeley National Library and Buck Institute made clear in a speech, cancerous stimuli often foster the development of senescent cells and, as discussed above, the Th1 pathogens are quite prolific during cancer.  But the greatest giveaway that senescent cells are at the mercy of the Th1 pathogens stems from the fact that, as Campisi described, senescent cells are metabolically active and secrete myriad inflammatory cytokines.  In my opinion, nothing screams infection more than the release of inflammatory cytokines, since the inflammatory molecules are released by the immune system in response to infection.  Campisi also described how, although senescent cells are targeted for clearance by the innate immune system, they are able to defy the immune response by secreting high levels of enzymes called matrix metalloproteinases (MMPs).  In my opinion, the creation of these enzymes probably marks yet another way the Th1 pathogens have evolved to alter cellular machinery in order to foster their survival.  

Then there’s stem cells.  If the rest of our cells can be infected by the Th1 pathogens, then why not our stem cells?  Or, can our stem cells be damaged by the cytokines secreted by other infected cells?  Indeed, Amy Wagers of Harvard University presented a talk in which she clarified that much of the aging process results when the stem cells can no longer repair the tissues.  Wagers stated that her work points towards “a discrete set of metabolic regulators and inflammatory cytokines which may alter the signals that stem cells receive from their environment in aged animals.”  Again, the fact that inflammatory cytokines seem to affect stem cell resiliency points to the involvement of chronic infection in stem cell decline. 

It got to the point where some of the talks were frustrating to watch because the data presented was so indicative of infection yet the researchers themselves kept missing the signs.  “They’re so close, but yet so far away,” Dr. Marshall commented at lunch.  I could sense the frustration in his voice.  
That most of the researchers at the Conference stand on the edge of better understanding their results in the context of the Th1 pathogens was best exemplified by a presentation given by Rita Effros of UCLA.  Effros actually presented data showing that chronic viral infection leads to an increase in senescent cells as well as significant decreases in telomere length.  Effros stressed how the constant effort that the body must extend in order to try to keep latent viral infections under control clearly detracts from the energy the body needs in order to effectively manage the waste products that damage the tissues.  Yet Effros is convinced that chronic viral infections cannot be eliminated and that, once present in a host, they cannot be stopped from causing an inflammatory response for the remainder of a patient’s life. 

Of course, those familiar with the Marshall Pathogenesis understand that latent viruses are simply co-infectious agents that are able to take advantage of an immune system greatly weakened by the Th1 pathogens.  So if the Marshall Protocol is used to eliminate the Th1 pathogens and innate immunity is restored, latent viral infections can indeed be quelled.  Nothing proves this reality more clearly than our own patient data (collected from the MP study site) which shows that viral co-infections disappear as patients reach the later stages of the MP.
   
Finally, after a brief coffee break, it was time for Dr. Marshall to speak.  I sat near the front, eagerly awaiting the audience’s reaction.  They seemed interested in all aspects of the talk.  But  when Dr. Marshall put up a slide showing the bacterial species detected from a shot-gun sequencing study on prosthetic hip joints and mentioned that one of the bacteria found was “thermal vent bacteria”, the audience cooed with intrigue. 

The slide showed that bacterial species such as Proteobacter, Methylobacter, and others have, only recently, been detected inside human tissues.  “These are bacteria never previously thought to exist in man,” Marshall stated.  “These are bacteria that nobody is looking for.”  And that’s exactly the point. 
The audience suddenly understood that, not just the aging community, but the medical community at large, is ignoring a vast microbiota of chronic pathogens – the pathogens that patients on the Marshall Protocol kill day-in and day-out, the pathogens that cause the inflammation linked to so many diseases of the aging, and very likely the pathogens that influence telomere length, senescence, stem cell resiliency, and the overall accumulation of the “junk” that contributes to the aging process.

Talking science with Dr. Marshall

Serendipitously, the talk after Dr. Marshall’s focused on centenarians, or people who live to be over 100 years of age and still maintain a relatively decent state of health.  The first slide, presented by Sonya Vasto of the University of Palermo showed a wrinkled, white-haired woman doing the splits.  The image made it quite clear that not everyone succumbs to diseases of the aging at the same rate.   Vasto’s team had spent several years tracking the children of centenarians.  Not surprisingly, the children of centenarians themselves often live to be older than the rest of the population.  I say not surprisingly because it was extremely obvious (at least to me!) that centenarians simply harbor very low levels of the Th1 pathogens.  And since they don’t have high chronic bacterial loads, they pass very few of the disease-causing bacteria to their children who, on the whole, also live longer, healthier lives.  

At least some members of the audience were able to make the connection since when the speech ended, Vasto was asked if, based on Dr. Marshall’s research, centenarians might have evolved stronger immune systems that are better able to combat the Th1 pathogens.  Again, the speaker was essentially forced to concede that she simply had not considered the possibility.

Other talks after Dr. Marshall’s discussed ways in which human beings might be able to better regenerate tissue.  One speaker discussed how researchers are manipulating tissue so that human beings who are victim to heart failure might be able to regenerate a new heart.  Exciting stuff!  But a little voice in my head kept repeating, “What exactly is the point of regenerating an organ if you haven’t corrected the disease process that caused the original organ to fail?”  Of course, I’m not talking about situations where people lose an organ due to acute injury.  I’m referring to a case in which someone loses a heart due to, let’s say, a heart attack. 

Will simply growing a new heart ameliorate the disease?  Absolutely not.  Unless the chronic bacteria that caused the first heart failure are killed, they will inevitably infect the second heart.  Not to mention that the blood vessels of the person with a regenerated heart are still infected with the Th1 pathogens and are still full of the plaque (largely made up of dead bacterial cells) that they generate.  So when one researcher put up a slide stating that cardiac regeneration might  “cure” cardiovascular disease, I silently and strongly took exception. 

I had the same reaction in response to a talk that discussed how the tissue of neonatal animals could be used to help patients with severe gastrointestional disease regenerate new stomach and intestinal tissue.  While I’m thrilled that the ability to regenerate tissue is a viable possibility, I strongly feel that, until regenerative researchers factor the Th1 pathogens into the picture, they will be endlessly perplexed by the fact that regenerated organs might fail much sooner than expected. Like the infected tissues they were grown to replace, they too will become victim to the Th1 pathogens.
 
The poster sessions – where I finally got a chance to present my poster “VDR Receptor Competence Induces Recovery from Diseases of the Aging ” – started at 9:00 pm on both Saturday and Sunday. I lost my voice on Saturday night because so many people wanted an explanation of the figures and molecular models on my poster.  On Sunday night I rested my voice in preparation for a larger crowd at my poster since I figured that Dr. Marshall’s speech had ignited an even greater interest in the MP.  And the crowds came.  I spoke to doctors, researchers and students, all of whom wanted an in-depth explanation of Marshall’s work.   Since returning from the Conference, I’ve already received numerous emails from many of the people at the poster session, asking more profound questions about the MP or simply informing me that they are planning to start the Marshall Protocol themselves.  

When I described the Marshall Protocol as an open-based internet study trial it was refreshing to see most people respond with looks of admiration rather than incredulity.  Whereas most of the researchers I have spoken with at other conferences and events (who were educated before the rise of the internet) are often uncomfortable using the words “medicine” and “internet” in the same sentence, the younger and more technologically savvy crowd at “Understanding Aging” seemed excited by the prospect that we are collecting data in a place where it can be viewed and accessed by millions. 
 
In the same vein, Dr. Marshall’s background in technology was seen as an asset to his work and, for many, seemed to increase the credibility of his research. De Grey also possesses a background in computer technology that again seems to have helped him view aging through a wider lens.   In my opinion, the fact that de Grey and Marshall are both technologically savvy and have both succeeded in running two of the most fast-paced and successful scientific movements is far from a coincidence.

I found the staff and board members of the Methuselah Foundation to be very friendly.  They approached me and made an effort to introduce themselves.  Several told me about the Mprize and wanted to know if Autoimmunity Research Foundation might want to take a stab at winning the competition.  Unfortunately, the Mprize is a contest that intends to reward any research team that can make a mouse live beyond its normal lifespan. 

I explained to several of the Methuselah staff that Autoimmunity Research Foundation will never win the Mprize because the chronic microbiota that cause inflammatory disease in humans are not the same pathogens that infect mice.  Furthermore, as discussed in this article, there are great differences between the Vitamin D Receptor homology of mice and men. 

Whereas in man the Vitamin D Receptor controls expression of the bulk of the body’s antimicrobial peptides that target the Th1 pathogens, the rat Vitamin D Receptor performs no such action.  Based on this knowledge, I hope that the Methuselah Foundation considers the possibility of creating an “Hprize” or a prize given to the research team that first allows a human being to live a longer-than-normal lifespan.  In my opinion, those patients on the Marshall Protocol are already headed to living longer, healthier lives. So if tracked over the next few decades, the entire cohort would win the “Hprize” hands down.

Meanwhile, based on people’s reactions to my poster, I could tell that many were capturing the full scope of Marshall’s research.  Happily, many people expressing the most interest were doctors.  I think I even convinced a neurologist who had previously considered CFS to be a psychosomatic disease of the MP’s validity. 

At the beginning of the Conference I had spoken with a gentleman who had literally pulled a bottle of vitamin D out of his pocket when I had started to discuss the vitamin D Receptor.  He had incorrectly assumed that anyone discussing vitamin D would naturally say something positive about the secosteroid.  But by the end of the Sunday poster session he let me know that he had ditched his vitamin D and was even considering the MP.  

Another doctor was so moved by Dr. Marshall’s speech that, during the dinner before the Sunday poster session, he cornered me in the salad line to let me know how excited he was about the MP’s implications. He said the MP reminded him of a particular Sherlock Holmes short story where Holmes figures out the killer’s identity by looking for a clue in the very place no one had considered. He was referring to an electron microscopy image Dr. Marshall showed during his talk, one of a cell infected by bacteria. The bacteria is inside the human cell– no one thinks to look there! I have seen few people so animated and I was so surprised by his exuberance that I dropped my tray (we were eating in a cafeteria) and my dish shattered on the floor.  Whoops! 

As the night wore on and people continued to swarm around my poster, I realized that although my main aim at the Conference was to spread word about the Marshall Pathogenesis, the energy at the Conference was also having a profound effect on me.  I’m excited that so many intelligent minds are working together to extend the human lifespan and, as an optimist, I think that defying death is within the realm of possibility. 

On the other hand, I think that the Aging Community ought to rethink their approach.  Before trying to lengthen our telomeres, we need to better understand why they become short in the first place.  And before trying to eliminate senescent cells, we need to figure out why they incessantly secrete inflammatory cytokines.  And before trying to regenerate organs, we need a full understanding of why an original organ went bad in the first place. 

In my opinion, all of the above have a single (historically elusive) common denominator: the Th1 pathogens.  And, as Dr. Marshall described in his talk, the tools to eliminate the Th1 pathogens exist here and now.  People can start to eliminate their bacterial loads today.  So as a first step, let’s eradicate the Th1 pathogens from the population.  Then let’s see how our telomeres, tissues, and cell-types respond to massive reduction in inflammation.  At that point, I know that de Grey and every researcher who spoke at the Conference will be able to push the boundaries of aging even further with optimal success.

Where was Dr. de Grey anyway?  I caught a glimpse of him out of the corner of my eye.  Standing near the entrance, wine glass in hand, he was laughing heartily, surrounded, of course, by a group of admirers.  If de Grey continues to push forward aging research as effectively as he did at “Aging 2008″, then he may very well live beyond the normal lifespan.  Yet even with the prospect at hand, he was clearly enjoying the current moment.  After all, that’s the key.  No matter how long we live, enjoying the here and now is what makes life worth living in the first place.  As the Argentine poet Borges once wrote, “Por si no lo saben, de eso esta hecho la vida, solo de momentos….” “In case you don’t know, that’s what life is made up, only moments.”  Except for my applause-worthy dropping of the dinner tray, all the moments I experienced at the Conference were good ones and, whether I live to be 50, 100, 1000, or 1,000,000 years old, I’m thankful for the chance to have shared that with so many new and open-minded people. 

Finally, here’s a short video the ARF put together from the conference. (If you have trouble loading this, try the smaller YouTube version.) Enjoy….

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For those who have access to a high-speed internet connection and fast computer, better version of this video, in High Definition is . Also available: the related abstract and Conference details.

The wear and tear created by the inflammatory response plays a large role in generating the stress and tissue damage that leads to old age.

In a 2006 paper in the Journal of Immunity and Aging, Italian researcher Sergio Giunta argues that inflammation and aging are intricately connected, to the point where the term “Inflammaging” has been coined “to explain the now widely accepted phenomenon that ageing is accompanied by a low-grade chronic, systemic up-regulation of the inflammatory response and that the underlying inflammatory changes are also common to most age-associated diseases.”

Essentially, the wear and tear created by the inflammatory response plays a large role in generating the stress and tissue damage that perpetuate old age and eventually death. Central to this response? According to Giunta, the release of cytokines, or proteins that generate pain and fatigue.

Although Giunta attributes this release of cytokines to the effects of “autoimmune” disease, those of us familiar with Marshall’s research and the emerging understanding of the role that bacteria play in chronic disease realize that, in reality, the cytokine release and subsequent persistent inflammation observed in inflammatory disease is likely the result of infection with a chronic intraphagocytic metagenomic microbiota (often referred to as the Th1 pathogens).

“We have shown much chronic inflammation results from the body’s innate immune response [to the Th1 pathogens], and we agree it seems likely that ‘Inflammaging’ may also result from this same pathogenesis,” Marshall argues in a letter published in response to Giunta’s article. “Clearly we still have a lot to learn about the processes which society categorizes as ‘aging,” argues the biomedical researcher.

Since the Th1 pathogens are found nearly everywhere in our environment, everybody picks up the chronic bacterial forms as they grow older; which species one acquires is largely related to one’s unique infectious history. As people accumulate the Th1 pathogens, many of them create substances that dysregulate the Vitamin D Receptor, thus disrupting several of the intricate feedback pathways that keep the levels of the two vitamin D metabolites (25-D and 1,25-D) in the correct range. 1,25-D goes up, and in the process, downregulates the level of 25-D in the body. Thus, a low level of 25-D is not a sign of “deficiency” but rather a strong indication that a person harbors a significant number of the Th1 pathogens.

If you were to graph the population’s 25-D levels on one axis and age on the other, the resulting graph would show that as a whole, the level of 25-D in the population drops steadily after age 40 – a clear indication that increasing age is correlated with a higher Th1 bacterial load. “Something is happening, even during ‘healthy aging’, that we really ought to understand a little more about,” says Marshall.

Not to mention the fact that as people grow older they increasingly succumb to diseases caused by the Th1 pathogens. “Our research points towards Th1 inflammation, the innate immune response to intraphagocytic pathogens, as being the cause of so many “diseases of the aging,” ranging from atherosclerosis, cardiomyopathy and arthritis through to many neurological conditions, and even to dementia,” states Marshall.

Stem cells

Bone marrow stem cells

Many of the cells damaged by cytokines are stem cells – cells that act as a repair system for the body by replenishing other more specialized cells. But as people age, stem cells often lose their ability to repair and heal.

Interestingly, there is a high probability that the Th1 pathogens may be able to infect stem cells. “The key consideration is whether the Th1 bacteria infect stem cells,” says Marshall. Dr Emil Wirostko of Columbia University, one of the foremost experts on chronic bacterial forms, died before he could publish on the subject. But according to his colleagues, Wirostko believed persistent bacterial forms are able to infect stem cells.

This scenario begs the question – do stem cells lose much of their ability to heal and repair due to the increasing load of Th1 pathogens that everybody accumulates over a lifetime?

Indeed, since the Th1 pathogens are intraphgocytic (they are able to survive inside the nuclei of cells) they can likely interfere with the processes of transcription and translation as well as hamper DNA repair mechanisms. “The body has a number of redundant repair mechanisms,” states Marshall. “Actually I should use the word complementary as that is a better description. These defense mechanisms are affected by the pathogens, as evidenced by accelerated aging of folks with Th1 diseases.”

Marshall describes how at a recent conference on Aging at the University of California at San Diego, he heard a presentation by a group of German researchers who had been studying the use of a patient’s own stem cells to repair heart tissue after a heart attack. Interestingly, the team discovered that people who had suffered a heart attack – an event which is most likely caused by certain species of the Th1 pathogens in the heart and blood vessels – possessed stem cells which were only about half as effective at repairing the heart tissue as stem cells transplanted from healthy 20 year-old males. This supports the view that infected stem cells lack many of the healing properties maintained by their healthy counterparts. “It wasn’t a surprise to me,” says Marshall. “Although it was a big surprise for the researchers…”

Telomeres

At both ends of every chromosome are telomeres made up of DNA base pairs, some of which are lost each time the cell divides.

New research suggests that the Th1 pathogens may also affect the aging process in ways not connected to the inflammatory response, namely by affecting sequences of DNA known as telomeres.

Our genes carry inherited blueprints of DNA sequences that determine our characteristics. Inside the center or nucleus of a cell, genes are located on twisted, double-stranded molecules of DNA called chromosomes. At both ends of every chromosome are stretches of DNA called telomeres – regions of highly repetitive DNA that essentially function as disposable buffers. These regions are of great importance because every time a cell divides, a small part of the DNA sequence at both ends of a chromosome is lost in the process – meaning that if telomeres didn’t exist, the main part of the chromosome – the part containing genes essential for life – would get shorter with each division.

Think of telomeres as the plastic tips on both ends of a shoelace. The plastic ends exist so that if the end of a shoelace gets damaged, shortened, or frayed, the soft cloth-like material that makes up the bulk of the shoelace will remain protected.

An enzyme named telomerase is able to add back bases to the ends of telomeres. Thus, in young cells, telomerase keeps telomeres from wearing down too much. But as cells divide repeatedly, the level of telomerase in the cell decreases, so the telomeres grow shorter and the cells age. When they get too short, the cell no longer can divide and becomes inactive or dies – meaning that the length of a person’s telomeres plays a role in how quickly they will age and eventually die.

Geneticist Richard Cawthon

Geneticist Richard Cawthon and colleagues at the University of Utah found that when people are divided into two groups based on telomere lengths, the half with longer telomeres lives five years longer than those with shorter telomeres – suggesting that if the people with the shorter telomeres could increase their telomere length to that of the people with longer telomeres, they could live five years longer.

In human blood cells, the length of telomeres ranges from 8,000 DNA base pairs at birth to 3,000 DNA base pairs as people age and as low as 1,500 in elderly people. (An entire chromosome has about 150 million base pairs.) Each time a cell divides, the average person loses 30 to 200 base pairs from the ends of that cell’s telomeres.

The fact that different people lose telomere base pairs at different rates suggests that factors other than simple cell division also impact how rapidly telomeres shorten. Increasing evidence is pointing to the fact that the Th1 pathogens may play a significant role in determining the rate at which these sequences of DNA are lost, thus revealing yet another way in which the chronic bacterial forms may impact the aging process.

For one thing, the DNA of pathogens has been found integrated with telomere DNA. And as Marshall describes, if pathogens do directly alter our DNA, then the weakened DNA at the ends of telomeres provides some of the easiest genetic material for them to mutate.

A number of studies have revealed that people who suffer from diseases likely to be caused by the Th1 pathogens often display shorter telomeres. These diseases include cancer, heart disease, and Alzheimer’s

For example, Cawthon’s study found that among people older than 60, those with shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

According to the Genetic Science Learning Center at the University of Utah, “Studies have found shortened telomeres in many cancers, including pancreatic, bone, prostate, bladder, lung, kidney, and head and neck.”

In 2003, researchers at the UCLA School of Medicine found that patients with Alzheimer’s disease had shorter telomeres when compared to control subjects without Alzheimer’s.

Telomere length as people age.

Similarly, the results of a recent study conducted by a team of researchers at the National Institute on Aging at the National Institutes of Health in Baltimore who assessed the telomere length of 41 people caring for loved ones with Alzheimer’s disease and 41 individuals matched by age who weren’t caring for an ill person. Caregivers had been looking after the Alzheimer’s patients for an average of five years. The fact that bacteria almost certainly drive the pathogenesis of Alzheimer’s is supported by a recent issue (May 2008) of Journal of Alzheimer’s Disease which was entirely dedicated to exploring the role of bacteria in causing Alzheimer’s.

The team reported in the Journal of Immunology that the telomeres of the Alzheimer’s caregivers were significantly shorter than those of the control individuals – suggesting that the Th1 pathogens from the Alzheimer’s patients had been transmitted to their caregivers over the course of the 5-year study period, shortening their telomeres in the process.

“So, it appears that in the patients with Alzheimer’s (and in the caregivers who are likely infected with the Th1 pathogens too), the telomeres are shortened,” says Joyce Waterhouse PhD of Autoimmunity Research Foundation. “I guess with our experience with the Marshall Protocol, we could conclude that Th1 disease and its associated inflammation cause this ‘premature aging.’” That view would go along with people seeming to get “younger” on the MP.

The fact that the caregivers displayed shorter telomeres does not necessarily mean that they will develop Alzheimer’s, although they may have a higher risk of developing other Th1 diseases associated with aging. In all cases, they should be comforted by the knowledge that the Marshall Protocol can prevent and reverse these illnesses.

Returning to the subject of shortened telomeres, it’s not surprising that researchers at Cedars-Sinai Research Institute and the University of California at Los Angeles also found shorter telomeres, suggesting premature aging, in patients with Lupus. A team from Homberg Germany came to the same conclusion in patients with T-cell lymphoma.

Futhermore, a variety of premature aging syndromes are associated with short telomeres. These include Werner Syndrome, Ataxia telangiectasia, Bloom syndrome, Nijmegen breakage syndrome and ataxia telangiectasia-like disorder. In all these diseases, genes have been mutated that affect telomere length in a manner yet to be determined.

What causes these genetic mutations? Pathogens are a likely candidate. Over thousands of years, bacteria, viruses, bacteriophages, and the Th1 pathogens have evolved mechanisms that allow them to mutate and alter the expression of the genes inside the cells they infect – meaning that the mutations observed in the above diseases could well be the result of bacterial infection.

Cawthon believes that if the telomere shortening process could be curbed, 10 to 30 years could be added to the average lifespan. Of course, the elimination of the Th1 pathogens won’t completely stop telomeres from shortening with cell division, but since these bacterial forms seem to accelerate the rate at which the telomere base pairs are lost, and everybody acquires significant levels of the Th1 pathogens as they grow older, it’s very possible that killing these bacteria could enhance the average lifespan.

What else does Cawthon implicate in aging? Oxidative stress, or damage to DNA, proteins and lipids (fatty substances) caused by oxidants, which are highly reactive substances containing oxygen. For example, in one study, scientists exposed worms to two substances that neutralize oxidants, and the worms’ lifespan increased an average 44 percent.

But consider this: what generates higher levels of these oxidants? According to Giunta, inflammaging. The inflammaging process generates Reactive Oxygen Species (ROS) – causing both oxidative damage and amplifying the number of cytokines released by the immune system. This perpetuates “a vicious cycle resulting in a….. state where tissue injury and healing mechanisms proceed simultaneously and damage slowly accumulates asymptomatically over decades and is a major determinant both of the aging process and of the development of age-associated diseases,” states Giunta.

But it is likely the Th1 pathogens that cause this “vicious cycle” – stimulating the immune system, which subsequently releases ROS and cytokines in an effort to eliminate them. Thus, when the bacteria causing this immune response are killed, the cycle, and the age-related damage that accompanies it, come to an end.

Nuclear Factor Kappa beta

Yet another way that the Marshall Protocol may affect the aging process is related to a chemical called Nuclear Factor Kappa beta (NF-kb). Just last week, scientists at Stanford University announced that they had successfully genetically altered mice so as to reduce the amount of NF-kB in their skin cells. Why? Because according to the researchers, the protein appears to control various aspects of the aging process.

The team used a lotion that inhibited NF-kB in the mice. After two weeks of treatment with this cosmetic, the skin of older mice displayed the look and genetic profile of younger skin. The skin also became measurably thicker.

Interestingly, the Th1 pathogens greatly contribute to the rise of NF-kB in the body. They are able to activate proteins that increase the activity NF-kB, which subsequently moves to the nucleus or center of an infected cell and stimulates the release of cytokines.

By reducing the level of the Th1 pathogens in the body, patients on the Marshall Protocol should also lower NF-kB and other inflammatory cytokines over time. Furthermore, Benicar, the medication that patients take along with the antibiotics, actually helps block the production of NF-kB.

“We know NF-kappaB is a product of Th1 inflammation, and Benicar is supposed to stop its production by blocking the Angiotensin II receptor,” says Marshall.

Of course the Stanford study was conducted on mice so it’s far too soon to generalize the effects of lowering NK-kB to human beings. Yet the study paves the way for a better understanding of how the proteins affected by the Th1 pathogens may contribute to the aging process.

Taking control of the body’s enzymes, receptors and hormonal systems

It is also becoming increasingly clear that the Th1 pathogens have, over millions of years, evolved the ability to directly alter the activity of the body’s hormones, enzymes and receptors.

A molecular model by Marshall showing a bacterial substance binding, and subsequently deactivating the VDR.

Marshall has isolated one species of bacteria capable of creating a molecule that binds and blocks the Vitamin D Receptor – a fundamental receptor of the body that controls not just the expression of thousands of genes, but the activity of the innate immune system and the production of the antimicrobial peptides. More bacteria with this same capability are likely to be identified in the coming years.

Thus, may be possible that at some point in every person’s life, it is inevitable that the bacteria they have accumulated will start to shut down the VDR, slowing the body’s ability to fight the pathogens responsible for causing the inflammation, oxidative stress, accelerated telomere shortening and perhaps other processes associated with aging.

If this proves to be the case, is the gradual deactivation of the VDR part of a natural process that gradually shifts every human being into the later phases of life, where the body loses its youthful resiliency?

After all, humans and bacteria have evolved side by side. Most of the cells in our bodies are not our own, they are bacterial. In fact, the bacteria in our bodies add up to more than 100 trillion cells. According to mainstream medicine, these cells are limited to our intestinal tract, but increasing evidence points to the fact that many bacteria also parasitize our other cells and live in biofilms within our tissues. Because our bodies are made of only some several trillion human cells, we are somewhat outnumbered by the pathogens.

With this in mind, is it possible that some of the trillions of bacteria are relatively harmless species involved purely in the aging process? According to Marshall, one could construct a hypothesis where relatively harmless species in biofilms have, over the course of millions of years, perfected the ability to gradually shut down the body’s receptors and hormonal systems as it ages.

The fact that an increasing number of people are developing diseases in which symptoms of aging appear earlier in life may simply be a reaction to vitamin D supplementation, immunosuppressive medications and beta-lactam antibiotics – all of which have allowed these bacteria to shut down the body’s hormonal control systems at a younger age.

Indeed, “premature aging” is a good way to describe the effects of increased inflammation, decreased telomere length, and the gradual deactivation of the body’s receptors. Those people who develop a full-fledged Th1 disease at a young age often complain of aches, pains, fatigue, brain fog, osteoporosis – all symptoms that are often considered “normal” in elderly people.

But people who suffer from diseases caused by the Th1 pathogens can now kill the bacteria causing “premature aging” by using the Marshall Protocol. Does this suggest that the elderly, who have accumulated similar forms of bacteria, or who harbor pathogens purely involved in the aging process, can also reverse the symptoms of aging by using the MP? It seems quite possible. Especially since, as described above, many patients who reach the later stages of the MP report feeling younger than when they started.

Consider that an infant not exposed to the Th1 pathogens in the womb begins life with a low pathogen load, no inflammation, little oxidative stress, telomeres that shorten at a slow rate, no VDR blockage, and healthy stem cells capable of efficiently repairing the tissues. Evidence so far suggests that patients who complete the MP regain these same attributes, thus returning to what could be described as a child-like state.

“Experts in the field of immunology are increasingly pointing to the fact that the aging of the immune system is a main factor influencing longevity,” states Dr. Greg Blaney. “As people grow older, their immune systems are forced to deal with higher bacterial loads, which in turn means they have to manage a greater inflammatory response. The MP downregulates this inflammatory response, restoring the agility of the immune system, which significantly affects the aging process.”

The Th1 pathogens may cause telomeres to shorten at a faster rate.

Obviously, it’s much too soon to draw any definite conclusions about the Th1 pathogens and aging as many of the potential roles that these pathogens play in the aging process are still based on speculation. And even if these intraphagocytic metagenomic bacteria are eliminated, who knows what other systems of the body may step in to circumscribe the human lifespan?

Then again, case reports from patients who have reached the late stages of the Marshall Protocol are highly encouraging. Once the Th1 pathogens have been killed, the body is demonstrating a remarkable ability to bounce back.

“We are also observing that the body has an amazing ability to regenerate after inflammatory damage which is currently considered to be ‘permanent’ (eg, fibrosis and peripheral neuropathy),” states Marshall.

In fact, progress reports are revealing that both physical and cognitive abilities are able to heal. “We have seen no sign that the brain doesn’t heal,” says Marshall. “The adults recover all their lost faculties as they heal on the MP, and the several children on the MP, who have had a variety of difficulties, also are recovering fully. So our data (at this point) shows that the body heals as bacteria are killed and immune function is restored.”