“I’m sixty going on sixteen.” “I think that at the moment my brain functions even better than it did when I graduated from college 50 years ago.” “I’m convinced that I will live longer because I’m doing the Marshall Protocol.” Comments like these - which were made by actual patients in the MP phase II study trial - are increasingly common as people reach the later stages of the treatment. In fact, many Marshall Protocol patients who have recovered from inflammatory conditions, such as sarcoidosis, rheumatoid arthritis, diabetes, and others report that recovery feels like “being 20 years younger.”

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.”^[1]

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.^[2] 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

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^[3] 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^[4][5] - 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

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 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.^[6]

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^[7][8], heart disease^[9][10], and Alzheimer’s^[11]

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.”^[12]

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.^[13]

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.^[14] 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.^[15] A team from Homberg Germany came to the same conclusion in patients with T-cell lymphoma.^[16]

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.^[17]

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.

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.^[2][18] 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.”

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.”

REFERENCES

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2. Marshall, T. G. (2007). Bacterial Capnine Blocks Transcription of Human Antimicrobial Peptides. Nature Precedings. [↩] [↩]
3. Erbs, S., Linke, A., Schächinger, V., Assmus, B., Thiele, H., Diederich, K., et al. (2007). Restoration of microvascular function in the infarct-related artery by intracoronary transplantation of bone marrow progenitor cells in patients with acute myocardial infarction: the Doppler Substudy of the Reinfusion of Enriched Progenitor Cells and Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) trial. Circulation, 116(4), 366-74. [↩]
4. Merline, J.R., Golden, A., & Mattman, L.H. (1971). Cell wall deficient bacterial variants from man in experimental cardiopathy. American journal of clinical pathology, 55(2), 212-20. [↩]
5. Higuchi-Dos-Santos, M.H., Pierri, H., Higuchi, M.D.L., Nussbacher, A., Palomino, S., Sambiase, N.V., et al. (2005). [Chlamydia pneumoniae and Mycoplasma pneumoniae in calcified nodes of stenosed aortic valves.] Arquivos brasileiros de cardiologia, 84(6), 443-8. [↩]
6. Cawthon, R.M., Smith, K.R., O’Brien, E., Sivatchenko, A., & Kerber, R.A. (2003). Association between telomere length in blood and mortality in people aged 60 years or older. Lancet, 361(9355), 393-5. [↩]
7. Mager, D. (2006). Bacteria and cancer: cause, coincidence or cure? A review. Journal of Translational Medicine, 4(1), 14. [↩]
8. Cantwell, A. (2004). Acid-Fast Bacteria In-Vivo in Prostate Cancer and the Connection between Prostate Cancer, Other Cancers, and the Kaposi’s Sarcoma Virus. Journal Of Independent Medical Research, 2(3). [↩]
9. Góis, J., Higuchi, M., Reis, M., Diament, J., Sousa, J., Ramires, J., et al. (2006). Infectious agents, inflammation, and growth factors: how do they interact in the progression or stabilization of mild human atherosclerotic lesions? Annals of vascular surgery, 20(5), 638-45. [↩]
10. Waterhouse, J. (2007). Two Views of Vitamin D Supplementation and Parathyroid Hormone. CISRA’s Synergy Health Newsletter. [↩]
11. MacDonald, A. B. (2007). Alzheimer’s disease Braak Stage progressions: reexamined and redefined as Borrelia infection transmission through neural circuits. Medical hypotheses, 68(5), 1059-64. [↩]
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13. Panossian, L.A., Porter, V.R., Valenzuela, H.F., Zhu, X., Reback, E., Masterman, D., et al. Telomere shortening in T cells correlates with Alzheimer’s disease status. Neurobiology of aging, 24(1), 77-84. [↩]
14. Damjanovic, A.K., Yang, Y., Glaser, R., Kiecolt-Glaser, J.K., Nguyen, H., Laskowski, B., et al. (2007). Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer’s disease patients. Journal of immunology (Baltimore, Md. : 1950), 179(6), 4249-54. [↩]
15. Kurosaka, D., Yasuda, J., Yoshida, K., Yoneda, A., Yasuda, C., Kingetsu, I., et al. (2006). Abnormal telomerase activity and telomere length in T and B cells from patients with systemic lupus erythematosus. The Journal of rheumatology, 33(6), 1102-7. [↩]
16. Widmann, T.A., Herrmann, M., Taha, N., König, J., & Pfreundschuh, M. (2007). Short telomeres in aggressive non-Hodgkin’s lymphoma as a risk factor in lymphomagenesis. Experimental hematology, 35(6), 939-46. [↩]
17. Madrigal, A. (2007). Genetic Cosmetic Makes Old Skin Like New. Wired. [↩]
18. Marshall, T. G. (2006). Molecular mechanisms driving the current epidemic of chronic disease. [↩]