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that lead to the removal of outdated cells in our body (apoptosis), thus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
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
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
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
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
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
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
"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,