The dream of any person is to stay young as long as possible. We do not want to get old and get sick, we are afraid of everything - cancer, Alzheimer's disease, heart attack, stroke ... It's time to figure out where cancer comes from, is there a connection between heart failure and Alzheimer's disease, infertility and hearing loss. Why do antioxidant supplements sometimes do more harm than good? And most importantly: can we live long and disease-free, and if so, how?
In our body, tiny "energy stations" - mitochondria - work. They are responsible for our health and well-being. When they work well, we do not lack energy. And when it's bad, we suffer from diseases. Dr. Lee Know reveals the secret: diseases that seem unrelated at first glance - diabetes, cancer, schizophrenia, chronic fatigue, Parkinson's disease and others - have a common nature.
Today we know how to improve the work of mitochondria, which provide the body with energy by 90%. In this book, you will find up-to-date information about nutrition, lifestyle, the ketogenic diet, and supplements that restore health to mitochondria, and therefore to us.
Excerpt. Mitochondrial syndrome
I'm embarrassed to admit it, but I was a viewer of the reality show "The Bachelor". I was very impressed with the third episode of season 17 (January 2013), in which Sin (bachelor) and Ashley (applicant) went to meet two girls suffering from mitochondrial disease. For many of you, if you watched the episode, this was your first exposure to mitochondrial syndrome (mitochondrial syndrome is a complex of diseases associated with congenital damage to the mitochondria). However, this group of diseases is being investigated more and more qualitatively as genetic testing and genetic sequencing technologies become simpler, cheaper and more accessible.
Until the early 80s, when the human mitochondrial genome was completely sequenced, reports of mitochondrial diseases were rare. The situation changed with the ability to decipher the mtDNA of many patients. This has led to a dramatic increase in the number of registered patients suffering from hereditary mitochondrial diseases. They include approximately one in five (or even two and a half) thousand people. Here we do not take into account individuals with unexpressed forms of mitochondrial diseases. In addition, the list of signs of the mitochondrial syndrome has grown sharply, which indicates the chaotic nature of these diseases.
Mitochondrial diseases are characterized by extremely complex genetic and clinical patterns, representing a mix of a very wide range of existing diagnostic categories. Inheritance patterns here sometimes obey and sometimes do not obey the laws of Mendel. Mendel described patterns of inheritance of traits through normal nuclear DNA genes. The probability of occurrence of a genetic trait or hereditary disease is easily calculated on the basis of a quantitative prediction of the results of splitting offspring for different qualitative traits by randomly inheriting one of the two copies of the same gene from each of the parents (as a result, each of the offspring receives two copies of each gene). In cases where the mitochondrial syndrome is due to a defect in nuclear genes, the corresponding inheritance patterns do indeed follow Mendel's rules. However, there are two types of genomes that make mitochondria work: mitochondrial DNA (passed only through the maternal line) and nuclear DNA (inherited from both parents). As a result, inheritance patterns vary from autosomal dominant to autosomal recessive, as well as to the transfer of genetic material through the maternal line.
The situation is further complicated by the fact that complex interactions are built between mtDNA and nDNA in the cell. As a result, the same mtDNA mutations can cause strikingly different symptoms in siblings living in the same family (they can have different nuclear DNA with identical mtDNA), while mutations can cause identical symptoms. Even twins with the same diagnosis can have radically different clinical pictures of the disease (specific symptoms depend on which tissues are affected by the pathogenic process), while people with mutations can suffer from similar symptoms that line up in the same picture of the disease.
Be that as it may, a large number of mtDNA variations exist in the maternal egg, and this fact invalidates all predictions regarding the results of genetic inheritance. The nature of this group of diseases is so chaotic that the set of symptoms corresponding to these diseases can change from decade to decade and differ even in siblings with identical mitochondrial DNA mutations. Moreover, sometimes the mitochondrial syndrome can simply disappear, despite the fact that it was (or should have been) inherited. But such happy cases are rare, and most often mitochondrial diseases progress. In table. Tables 2.2 and 2.3 present the diseases and symptoms associated with mitochondrial dysfunction, as well as the genetic factors behind these diseases. Over 200 types of mitochondrial mutations are currently known to science. Research suggests that many degenerative diseases are caused by mutations of this kind (meaning that we have to reclassify a huge number of diseases into the category of mitochondrial diseases).
As we know, these mutations can cause mitochondria to stop performing their energy-producing function, causing cells to stop working or die. All cells (with the exception of red blood cells) contain mitochondria, and, accordingly, the mitochondrial syndrome affects multicomponent and very different body systems (simultaneously or sequentially).
Table 2.2. Signs, symptoms and diseases caused by mitochondrial dysfunction
Table 2.3. Congenital diseases caused by mitochondrial dysfunction
Of course, some organs or tissues need energy more than others. When the energy needs of a particular organ cannot be fully met, symptoms of the mitochondrial syndrome begin to appear. First of all, they affect the functions of the brain, nervous system, muscles, heart, kidneys and endocrine system, that is, all organs that require a large amount of energy for normal operation.
Acquired diseases caused by mitochondrial dysfunction
As our understanding of mitochondrial function and dysfunction grows, we begin to create a long list of diseases based on mitochondrial dysfunction and to elucidate the mechanisms by which these diseases arise and develop. The data of some recent studies indicate that every 2500th person suffers from mitochondrial syndrome. However, if you carefully study the list below, you will agree that with a high degree of probability, mitochondrial diseases (congenital or acquired) will soon be recorded in every twenty-fifth or even one in ten Westerners.
- Diabetes Type II
- Cancer
- Alzheimer's disease
- Parkinson's disease
- bipolar affective disorder
- Schizophrenia
- Aging and decrepitude
- Anxiety disorder
- Non-alcoholic steatohepatitis
- Cardiovascular diseases
- Sarcopenia (loss of muscle mass and strength)
- exercise intolerance
- Fatigue, including chronic fatigue syndrome, fibromyalgia, and myofascial pain
At the genetic level, very complex processes are associated with all this. The energy strength of a particular person can be determined by examining congenital disorders of his mitochondrial DNA. But this is just a starting point. Over time, acquired mtDNA defects accumulate in the body, and after an organ crosses a certain threshold, it begins to act up or becomes prone to degeneration (each organ has its own tolerance threshold, which we will discuss in more detail).
Another complication is that each mitochondria contains up to ten copies of mtDNA, and each cell, each tissue, and each organ has many mitochondria. It follows from this that in our body there are countless defects in mtDNA copies. The dysfunction of a particular organ begins when the percentage of defective mitochondria living in it exceeds a certain value. This phenomenon is called the threshold effect36. Each organ and each tissue is subject to specific mutations and is characterized by its own mutational threshold, energy requirements and resistance to free radicals. The combination of these factors determines the reaction of a living system to genetic disorders.
If only 10% of mitochondria are defective, 90% of the remaining normal cellular energy generators can compensate for the dysfunction of their "colleagues". Or, for example, if the mutation is not very serious, but affects a large number of mitochondria, the cell can still function normally.
There is also the concept of defective mitochondrial segregation: when a cell divides, its mitochondria are randomly distributed between two daughter cells. One of these cells can get all the mutated mitochondria, while the other can get all the full-fledged "power plants" (of course, intermediate options are more likely). Cells with dysfunctional mitochondria will die in the process of apoptosis, while healthy ones continue to do their job (one of the explanations for the sudden and unexpected disappearance of the mitochondrial syndrome). The phenomenon of differences in the DNA sequence of mitochondria (or plastids) in the same organism, often even in the same cell, when some mitochondria, for example, may contain some kind of pathological mutation, while others do not, is called heteroplasmy. The degree of heteroplasmy differs even among members of the same family. Moreover, the level of heteroplasmy can vary even within the same organism depending on a particular organ or a particular cell, which leads to a very wide range of manifestations and symptoms of a particular mitochondrial disease.
In the body of a growing embryo, as cells divide, mitochondria with mutations fill organs and tissues that differ from each other in terms of their energy needs. And if mutated mitochondria in large numbers inhabit cells that eventually turn into metabolically active structures (for example, the brain or heart), then the corresponding organism has problems with the quality of life (if it is viable at all). On the other hand, if a mass of dysfunctional mitochondria accumulates primarily in cells with a low metabolic rate (say, in skin cells that regularly replace one another), then the carrier of such mitochondria may never know about their genetic predisposition to mitochondrial syndrome. In the episode of The Bachelor mentioned above, one of the girls with mitochondrial disease seemed quite normal, while the other was clearly suffering from a serious illness.
Some mitochondrial mutations develop spontaneously with age as a result of the generation of free radicals during normal metabolism. What happens next depends on a number of factors. For example, if a cell filled with dysfunctional mitochondria divides at a high rate, as do stem cells that perform the work of tissue regeneration, then defective energy generators will actively carry out their expansion. If the weakened cell no longer divides (suppose we are talking about a neuron), then the mutations will remain within the limits of only this cell, which, however, does not exclude the possibility of a successful random mutation. So, it is precisely the complexity of the genetic basis of the mitochondrial syndrome that explains the fact that the depletion of the body's bioenergetic resources caused by mitochondrial mutations manifests itself within a wide range of diverse and complex diseases and symptoms.
We must also remember that there are many genes outside of mtDNA that are responsible for the normal functioning of mitochondria. If the mutation affects the genes encoding RNA, then the consequences are usually very serious. In those cases when a child receives a mutated mitochondrial transcription factor at his conception from any of the parents (recall that transcription factors are proteins that control the process of mRNA synthesis on the DNA matrix by binding to specific DNA regions), then all mitochondria of his organism. However, if the mutation refers only to specific transcription factors that are activated only in certain organs or tissues or in response to the release of a specific hormone, then the corresponding pathogenic effect will be exclusively local.
A wide range of mitochondrial diseases and their manifestations is a serious problem for physicians (both theoretical and practical), including the actual impossibility of predicting the development of mitochondrial syndrome. There are so many mitochondrial diseases that it's hard to name them all, and many of them have yet to be discovered. Even a number of well-known degenerative diseases (diseases of the cardiovascular system, oncological diseases, various forms of dementia, etc.) are attributed by modern science to mitochondrial dysfunction.
It is important to realize that while there is no cure for mitochondrial diseases, many people with these diseases (especially those with mild or moderate disease) can live long and full lives. However, for this we need to work systematically, using the knowledge that has appeared at our disposal.
About the Developer
Lee Know is a licensed naturopathic doctor from Canada, winner of several awards. Colleagues know him as a visionary entrepreneur, strategist and physician. Li has served as a medical consultant, scientific expert, and director of research and development for major organizations. In addition to his scientific work for his company, he is also a consultant for natural health products and nutritional supplements, and serves on the editorial advisory board of Alive, Canada's most widely read health magazine. He calls home the Greater Toronto Area, where he lives with his wife and their two sons, and is particularly interested in promoting natural health and protecting the environment.
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Source: habr.com