As a student of biological aging since 2005, I have seen many theories of aging, including the ever-so-popular free radical, mitochondria, and DNA damage theories of aging.
However, my gut feeling is that these theories, as wonderful as they may sound on paper, may not be giving us the FULL PICTURE of the aging process in a way that allows us to intervene effectively to reverse the aging process for infinite human lifespan.
I mean, they may be accurate, and they may be true. But are they giving us the FULL PICTURE? Is an accurate understanding of cellular aging the same thing as an accurate understanding of organismal aging?
How sure are we that by reversing aging in cells, we also harmoniously reverse aging of the organism? Or is the aging of cells merely a reaction that the cells have toward something else within the organism that is the actual root cause of aging?
I have always had the fear that when one holds onto a theory for too long, it eventually becomes dogma. No matter how great a theory is, it will always be part of a BIGGER PICTURE.
As such, I would like to suggest a different perspective on aging. It is one that I have heard about from no one else. It is a unified theory of aging that seems to explain all other theories of aging that I have so far encountered, including: (1) free radical theory, (2) mitochondrial theory, (3) DNA damage theory, (4) telomere theory, (5) stem cell theory, (6) neuroendocrine theory.
Recently, I have come across some new discoveries in the field of aging. These new discoveries embody an emerging field called “immunosenescence”. Immunosenescence is not a theory of aging per se. Rather, it seems to be embraced by people who consider the breakdown of the immune system to be at the “center stage” of the aging process itself.
My ventures into the world of immunosenescence have ignited a burning flame within my mind that just will not go away. Its ideas have triggered a unified theory of aging that seems to explains all other theories of aging.
Consider the following points:
Point #1:
All degenerative diseases of aging, including cancer, heart disease, atherosclerosis, multiple sclerosis, Alzheimer's, and diabetes, appear to be caused by pathogenic microbes. Now, before you cry “heresy”, let me point out that a significant percentage of all cancers are confirmed by the mainstream research establishment to be caused by microbes: cervical cancer (papillomavirus), stomach cancer (helicobacter pylori), liver cancer (hepatitis B), Burkitt's lymphoma (Epstein Barr virus). Epstein Barr virus has also been implicated in Hodgkin’s disease, non-Hodgkin’s lymphoma, nasopharyngeal carcinoma, leiomyosarcomas, and epithelial malignancies [ http://clincancerres...t/10/3/803.full ].
But it's not just cancer. Heart disease appears to be caused by cytomegalovirus. Alzheimer's appears to be caused by an intracellular bacterium called chlamydia pneumoniae. Rheumatoid arthritis appears to be caused by Proteus bacteria, while Crohn's disease appears to be caused by subclinical bowel infections with Klebsiella microbes [ http://www.hindawi.c...ad/2012/539282/ ].
Point #2:
Microbes are everywhere in our environment, regardless of how “sterile” we think it is. There is a whole universe of microbes floating through our air that, until recently, have remained undiscovered by modern science. In fact, according to a New York Times article published in 2007, NASA has recently discovered that even in the most “sterile” environments previously thought to be 100% free of bacteria, there are actually HUGE QUANTITIES of bacteria that cannot be detected by modern-day methods of bacterial detection like cell culturing. Using a radical new method called ribosomal RNA gene sequence analysis, NASA had detected almost 100 different types of bacteria, in huge quantities, in all of its so-called “clean rooms” previously thought to be among the most sterile environments in the world [ http://www.nytimes.c...9clea.html?_r=0 ].
And I guess I do not have to remind you that our digestive systems are “swimming” with vast quantities of both “good” and “bad” bacteria that have persisted since the day we were born, and that all it takes is a minor imbalance in our immune systems to allow some of the “bad” bacteria to cross over into other parts of our bodies to cause harm and disease.
Point #3:
We are all suffering from chronic, low-grade infections that gradually increase with age. In addition, we never fully “get over” an acute infection or illness, especially a viral infection. Whatever major infectious illnesses you've had in the past, you are probably still battling it right now, albeit in a low-grade manner. In the field of immunosenescence, it is generally recognized that inflammatory biomarkers steadily increase with age.
Point #4:
Certain types of viruses permanently modify the chromosomal DNA of our stem cells through latent viral infection. These permanently altered stem cells then pass on the viral genes to their progeny. Some of these viral genes cause cellular senescence, while other viral genes cause abnormal cell replication that can lead to hyperplasia or cancer. Either way, all viral gene infections cause inflammation. This means that all of the stem cell's progeny can become either senescent or carcinogenic, as well as inflammatory. Entire areas of tissue can become senescent or carcinogenic from a single latent viral infection of a single stem cell. And viruses are everywhere! Remember, these chromosomal DNA changes are permanent and cannot be corrected through natural means. That is, they persist indefinitely. Over time, these viral stem cell infections accumulate as the organism “ages”.
Thus, viruses alone are adequate to explain the aging of entire tissues. But there's more...
Point #5:
Hematopoietic stem cells, the stem cells that give rise to all cells of the immune system, are the known target of at least several different viruses, including Human Herpes Virus (HHV)-6, Human Cytomegalovirus (HCMV), Measles virus, and the well-known HIV virus. This may age the immune system, which in turn, allows other pathogenic microbes to infect the hematopoietic stem cells, which in turn, further ages the immune system, which in turn, allows even more pathogenic microbes to infect the hematopoietic stem cells, as a vicious cycle toward the eventual death of the organism ensues.
The HIV virus, in particular, is known in the research community as a virus that appears to accelerate the human aging process. You heard me right. HIV appears to accelerate human aging. But don't take my word for it. Google the words, “HIV accelerated aging”.
Point #6:
Germline cells may be immune to viruses, as their cell surfaces may be void of virus-friendly receptors. Thus their DNA would be protected from viral senescence genes. This protects the species from instantaneous extinction.
Point #7:
Some pathogenic microbes can evade the immune system, regardless of how young or strong the immune system is. These include latent viruses such as cytomegalovirus, intracellular bacteria such as chlamydia pneumoniae, and nanobacteria (responsible for tissue calcification). This means that, even if you rejuvenate every cell of the body including immune cells, the organism will still eventually die of pathogenic microbes as they spread unimpeded.
Pathogenic microbes evolve faster than metazoan life forms such as humans, animals, and plants. HIV is a prime example of such fast evolution. Thus pathogenic microbes will always outcompete and overtake metazoan life forms.
Point #8:
As the immune system battles more infections, the pool of mature CD8+ T cells expands with age. Unfortunately, the pool of naïve CD4+ T cells diminishes, leaving the body vulnerable to new infections. This is irreversible. So even if you rejuvenate every cell of the body, this issue still needs to be resolved, and it is not a simple matter of cell rejuvenation.
Point #9:
Aging is inflammation, and inflammation is aging. All senescent cells are inflamed cells. All senescent cells express high levels of NF-kappaB. NF-kappaB is known for its role as the master signal of inflammation.
Inflammation causes free radicals and damage to cellular structures such as mitochondria, as the cell prepares to die through apoptosis. The free radical, mitochondria, and DNA damage theories of aging may be part of a bigger picture with inflammation at the center stage.
Fortunately, once the source of inflammation is removed, including removal of viral genes, the cell regains its normal operation. That is, it is no longer senescent.
Putting It All Together
So the unified theory is that pathogenic microbes ultimately cause all aging in humans, animals, and plants. Free radical damage, mitochondrial damage, and DNA damage are merely symptoms of inflammation that is ultimately caused by microbial infection. Infection of stem cells and their stromal niche cells fully explains all the symptoms reported by proponents of the stem cell theory of aging, where niche cells fail to secrete signals, and stem cells fail to respond to signals from the niche cells [ http://onlinelibrary...6/S0378-1097(03)00643-8/pdf ]. And under chronic inflammation facilitated by NF-kappaB, the TERT gene (telomerase reverse transcriptase) becomes methylated, preventing transcription factors from binding to TERT. This answers the mystery of why stem cells, which when young had expressed high levels of TERT, no longer express TERT as the organism ages, which also explains why and how stem cells age.
It is well known that aging is stochastic rather than uniform among a population of cells within a tissue. That is, given a population of tissue cells, a certain percentage of the cells are always senescent while the remaining cells are not. It may be because those senescent cells are directly or indirectly infected with pathogen. The “scheduled” stem cell turnover of tissues may be a compensatory mechanism by stem cells to keep tissues as young as possible, for as long as possible. It is worth pointing out that senescent cells are normally cleared out by macrophages, which are cells of the immune system, and that senescent cells always secrete pro-inflammatory cytokines. These inflammatory, cytokine-secreting, immune-system-attracting, senescent cells are probably infected with pathogen, for, as the saying goes, “If it walks like a duck, if it quacks like a duck, if it looks like a duck, then chances are, it's a duck.”
I have read somewhere that plants wither and die due to microbial infection. The nematode worm, C. elegans, typically dies of bacterial infection. The fruit fly, Drosophila melanogaster, typically dies with major inflammation of the digestive tract at the moment of death [ https://www.fightagi...d-flies-die.php ]. Laboratory mice typically die of cancer, which has been linked to viruses. And prior to the discovery of antibiotics, humans have often died of acute infections such as pneumonia. The list goes on and on.
The Solution
A suggested solution is: (1) Eliminate pathogens, (2) Reverse or nullify viral genes, or any other permanent and heritable damage, from stem cells, especially hematopoietic stem cells, or even more importantly, pluripotent stem cells such as VSELs (Very Small Embryonic-Like stem cells) or MIAMI cells, (3) Free up naïve T-cell space by eliminating a large percentage of mature T cells through such methods as, for example, targeted apoptosis.
Item (2) can be done by replacing the existing stem cells with young stem cells derived from induced pluripotent stem cells, which in turn, are derived from pristine germline cells unadulterated by viral infection. Young stem cells tend to outcompete old stem cells for niche space, so this should be a matter of simple intravenous injection of the young stem cells into the body.
Your Opinion
What is your opinion? I'd like to know...
