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"My Genes, My Health" Strategy
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by Prof. Dr. Chris De Bruijn, MedPlus Europe S.A.
06 the future of Medicine
Aging, chronic immune stimulation and chronic degenerative disease are logic consequences of life. Our genes and our life style can influence aging. Modern molecular medicine for the first time offers options to use that knowledge.
Aging is a normal biological process. It is the logic consequence of the fact, that we can only exist and survive thanks to the use of the oxygen that we breath and the interaction with other substances (e.g. food). During the processing of oxygen and food, highly oxidative molecules, called "free radicals", are formed. They have a number of important biological functions, a. o. in the regulation of the blood pressure, in supporting the immune system in its fight against micro-organisms and in the processes that lead to the removal of outdated cells in our body (apoptosis), thus enabling "fresh" cells to take over.
However, if the activity of free radicals is not carefully enough kept under control, they can do much more, than what normally would be their biological function: they can damage biological molecules that are important for the functioning our cells and impair their function.
In order to limit the damaging effects of free radicals, evolution has developed a whole battery of "anti-free-radical" (or: "anti-oxidative") strategies, including damage repair mechanisms, anti-oxidative enzymes, nutritional compounds, such as anti-oxidative vitamins and plant-derived substances.
It has been shown, that even the most efficiently operating anti-oxidative system will still let "escape" a few percent of the free radicals that originate during normal oxygen metabolism. Moreover, during lifetime, the efficacy of our anti-oxidative mechanisms continuously decreases (less efficient repair enzymes, which is genetically determined, or less intake of antioxidants with the food, which we can influence ourselves).
Mental stress, infections, negative environmental and life style factors, leading to impaired blood circulation (hypoxia, acidosis) can weaken the efficacy of the health enhancing and life saving anti-oxidative system. Such a situation of unwanted hyper-activity of free radicals is called "oxidative stress".
The immune system / brain network
One of the most important consequences of prolonged oxidative stress is, that the "maintenance system", that guarantees the integrity of our body functions (the "immune / brain network"), is continuously in an "alarm" situation. When it comes to the brain, this can lead to mental dysfunction (e.g. depression) and as far as the immune system is concerned, this can lead to a variety of chronic imbalances in the function of various immune cells, with stimulation of certain cells and inhibition of other cells, but always with a less adequately functioning immune system as a consequence. Disturbed immune balances are generally associated with mental dysfunctions, such as depression, and also the reverse is true, since brain and immune system operate as one functional unit.
Thus, a variety of external factors, many of which we can control, can cause chronic immune stimulation, damage important cellular structures and decrease of physical and mental capacity.
This is, what is called "the aging process"
In case of a badly controlled, accelerated aging process, degenerative mechanisms will cause certain body functions to deteriorate more rapidly and chronic disease states may develop.
External factors are not the only promoters of chronic immune stimulation and degenerative processes. Genetic factors play an at least as important role.
The possibility of identifying individual gene variants (polymorphisms), that predispose to an increased risk for a chronically stimulated immune system, associated with accelerated aging and chronic diseases, has recently become a realistic option.
There is substantial evidence, that naturally occurring variants of such variant genes (so-called single nucleotide polymorphisms, SNP´s; see below) confer individual susceptibility to the development of a certain disease-prone phenotype (for instance, gene variants that are associated with a lowered anti-oxidative capacity, leading to a decreased resistance in cases of oxidative stress and accelerated aging processes), even though there is only a minimally altered function of the variant gene products. This means, that genetically predisposed persons may age more rapidly and develop more easily a chronic degenerative disease than other persons.
Since 1986, we have shown that chronic immune stimulation, such as during chronic subclinical infections, cancer, autoimmune disorders and food intolerance, is indeed associated with behavioural symptoms similar to those seen in the context of chronic stress and major depression. These findings have been confirmed by many other groups and the immunological aspects of chronic disease states are receiving more and more recognition, even from the side of conventional mainstream medicine.
Both the brain and the immune system produce signal substances (e.g. cytokines, neuropeptides, neurotransmittors) that can be "read" by both immune cells and by cells from the central nervous system: everywhere in the "immune system / brain network "the same language" is spoken.
The so-called "cytokine network" is responsible for the bi-directional exchange of information between the brain and the immune system. A major role in the regulation of this cytokine network is played by the T-helper (Th) lymphocytes, in cooperation with other types of immune cells, such as T-suppressor cells, macrophages and natural killer cells. This has extensively been documented in individuals with acute and chronic stress, major depression, chronic inflammation and chronic infection.
Changes affecting one part of this network (e.g. disturbance of immune balances in chronic immune stimulation) have always consequences for the other part (e.g. by causing alterations in brain functions). Also the opposite is true: events in the brain (e.g. changed neuropeptide activity during mental stress) have a profound impact on the balances between the immune cells that produce cytokines.
Under normal conditions, low (physiological) levels of cytokines allow the maintenance of the reactivity and flexibility of the nerve cells (neurons) in the brain. But excessive and sustained imbalanced production of the wrong cytokines is likely to impair both neuronal and non-neuronal cell functions. Therefore, it is not surprising, that abnormal cytokine levels in the central nervous system are associated with several human diseases, including major depression and Alzheimer´s disease.
Novel options for treatment and prevention of chronic diseases
Because the immune system and the nervous system form one functional unit, a chronic immune imbalance is mostly also associated with a mental imbalance: psycho-neuro-immunological (PNI) diseases, including major depression and chronic fatigue, autoimmune diseases (such as rheumatoid arthritis and multiple sclerosis), cardiovascuar diseases and malignant diseases are invariably associated with a chronically stimulated immune system.
It has been shown, that restoration of the proper immune balances not only offers novel effective therapeutic, but also novel preventive options for these conditions.
As has been noted above, the mechanisms, by which a chronically stimulated immune system causes a chronic disease, may vary considerably from individual to individual. They depend on the individual genetic predisposition and on personal environmental and life style factors. Consequently, a new approach that integrates these factors will be more successful than the monodisciplinary, organ-oriented strategies followed by conventional medicine thus far.
Immune balance and mental depression are considered as factors that mutually influence each other. Therefore, depression is receiving more and more attention as a signal of an impairment of the immune system / brain network and can be interpreted as an indication of a chronically disturbed homeostasis. In other words:
depression can be seen as an "early warning" signal of chronic degenerative disease. In what clinical form such an "aging" disease will become expressed, is dependent on individual genetic and environmental factors
Many studies in humans have demonstrated the influence of mental stress on the susceptibility to infections (including HIV, Chlamydia and CMV infection) and on survival in malignant diseases. In autoimmune diseases, depression, as well as a particular sensitivity to stressful events, seem to modify the course of conditions, such as rheumatoid arthritis and Sjögren´s disease. As a rule, a better condition of the immune parameters is associated with a more favourable clinical course.
Conversely, impairment of immune function, such as during chronic infection, cancer and autoimmune disorders, is associated with the development of behavioural symptoms similar to those seen in the context of chronic stress or major depression.
Nutritional compounds are known to have a considerable impact on the immune balance. On one hand this concerns anti-oxidative nutrients, such as vitamins, plant metabolites (including bioflavonoids) and certain minerals, such as selenium. These nutrients are known to downregulate the expression of "wrong" cytokines. Therefore, nutritional analysis is an important factor.
The Gene Connection
Recent research shows, that many genes are present in variant forms in the human population. These variants have very small structural differences, for instance just one single nucleotide out of the several hundred nucleotides that form a gene.
Such variant forms (single nucleotide polymorphisms; SNP's) give rise to proteins with a slightly different structure. A variant protein may work satisfactorily under normal conditions, but when it gets under pressure (for instance, in case of a chronic infection or during the metabolism of certain food components or medicaments), it might perform less adequately and cause an imbalance in the regulating mechanisms of the major "maintaining system" of the body. If not brought back to balance properly, this may ultimately lead to disease. Every human being carries a number of such variant genes and this explains, why exactly the same factors can nevertheless cause different reactions in different people.
Only recently, we have begun to understand, how the interaction between an individual and the environment, including nutrition, infections etc., is under the influence of these gene variants. They are for a significant part responsible for what is called "genetic predisposition".
In order to understand the actual health situation (the so-called phenotype) in view of the development of individualised strategies for treatment or prevention, the combination of gene testing and data on individual immune balance and metabolic performance is needed.
1) MedPlus / EURIMM´s "My Genes, My Health" approach combines the analysis of genetic predisposition by means of gene variant testing ("genotyping") with an in depth analysis of the functioning of the immune system / brain network and metabolic profiles ("phenotyping").
2) This novel approach allows the establishment of an integral picture of an individual´s personal health situation and makes it possible to - on the molecular level - design a personalised anti-aging and wellness strategy.
3) Since chronic diseases show the characteristics of unbalanced, accelerated aging processes, the "My Genes, My Health"- approach can not only be used for the prevention of aged-related health concerns: it has been proven to be highly successful in the treatment of chronic disease states, including chronic fatigue immune deficiency syndrome, fibromyalgia, autoimmune diseases (e.g. rheumatoid arthritis, multiple sclerosis), infectious bacterial and viral diseases, food intolerance, cardiovascular diseases and cancer.
4) The unique point of the "My Genes, My Health" - concept is the view that "Body" and "Mind" are part of one and the same integral network ( immune system / brain network) and that the molecular analysis of the bi-directional exchange of genetic, immunologic and metabolic information within this network provides completely new perspectives to prevent and treat health concerns in an holistic, evidence-based way.
It is this integration of data obtained from the genotypic and phenotypic analysis mentioned above and its application to the individual situation of a given person, that provides the
basis for the "My Genes, My Health"concept
"Genetic predisposition, immunological and metabolic functions as key elements for personalised treatment and prevention of processes that cause chronic disease".
Please also take a look at the:
Club of Amsterdam Forum
and the conference about
'the future of Medicine - The Patient Experince'
on May 28, 2003
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