12 November 2008

Lifestyle Genetics

The genes we changeOleg Senkov, "In the World of Science" No. 11-2008

At the moment when you hold this issue of the journal "In the World of Science" in your hands, each of your 20 thousand genes, packed somewhere in one of the 46 chromosomes of any somatic cell of your body, oscillating, is in completely different states, depending on how you read this article. Whether you drink tea, coffee or pomegranate juice while sitting at home or in the office, or rush in a crowded subway car, trying your best to keep your balance and read at the same time, straining almost all of your 656 muscles. And certainly your genetic status has become completely different now compared to what it was, say, tonight, when you were asleep, yesterday – when you spent half a day driving a car, or three days ago, after a fun weekend, not to mention what happened a month, a year, five years ago.

Perpetuum mobile – everything changes and stays in perpetual motion! Strange as it sounds, but our genes are also constantly changing. No, not the information encoding proteins itself, recorded in the form of a nucleotide sequence of DNA (however, this also happens during point mutations, chromosomal aberrations, deletions and insertions, becoming the basis of gene evolution, as well as many gene diseases), but the state of the genes – they are activated, then inhibited, and until they are completely turned off. The expression of some of them in the cell can increase smoothly, abruptly or according to some other complex scheme, others at the same time - to fade away or stay at a certain basal level. And all this can happen within moments, or from a few minutes to hours, sometimes days. Each of our genes has its own inherent status quo, which depends on thousands of different factors, both internal and external. And it takes very little to change it, often so little that you are amazed at how sensitive genes are to our actions, to what we ate or drank, what air we breathed, how we slept, rested or how actively we spent the day, even to what we thought and dreamed about, what we mentally worked on they worked hard or that they were emotionally worried. Everything affects to one degree or another, sooner or later, directly or indirectly. The gene is no longer seen as a closed "black box" – it is a fairly open system that subtly senses ourselves and the environment. Of course, each cell, like a small factory, produces its own set of proteins and proteins inherent only to it; a neuron cannot suddenly be forced to express digestive enzymes of the pancreas, although it has all these genes, only they are blocked, just as pancreatic cells cannot be forced to synthesize proteins of the myelin sheath of axons or specific synaptic macromolecules of neurons. Everything is predetermined in the process of embryonic development. But an invisible conductor can manage a complex orchestra of several thousand synthesized proteins that each cell expresses every minute – you and I, our lifestyle plus environmental factors.

Scientists have long noticed that identical twins born with exactly the same set of genes differ from each other in many ways, for example, predisposition to diseases, especially such as schizophrenia, depression or bipolar affective disorder, often have different characters and habits, even anthropomorphic body indicators may be different. And the older the twins, the more the conditions and the way of their life diverge, the more pronounced this disparity becomes. It turns out that the environment, personal experience, behavior, habits, nutrition, etc. largely determine ourselves, our global molecular genetic picture of the organism - which genes are expressed, where and how, and which genes "sleep". For example, if one of the twins has cancer, the chances of the other getting sick are only 20%, which shows how minimal the influence of genes per se, and high – environment, individual experience. Or another example: epidemiological studies of the last 50 years have shown that the incidence of malignant tumors of the lungs, rectum, prostate and breast is much higher in Western countries than in eastern ones; and vice versa, brain, neck and uterus cancers are common in India, and stomach cancer is common in Japan. Moreover, the migration of people completely changes this picture: migrants begin to get sick with diseases of the country where they arrived. Again, there is a powerful environmental factor. Today, experts believe that the influence of the genes that we inherit on the development of chronic diseases is only 15%, the remaining 85% is the "merit" of our lifestyle. In the English–language scientific literature, a term such as lifestyle diseases has recently appeared - lifestyle diseases, which now include diabetes, obesity, many cardiovascular diseases, asthma, atherosclerosis, strokes, hypertension, hormonal, digestive and immune system disorders, Alzheimer's disease, depression and phobias, even cancer.

Today, scientists identify six main factors that directly affect the expression pattern of our genes: food, diet, physical activity, stress level, bad habits, environment (ecology). All these factors, in addition to genetics, are responsible for how healthy we are. As water sharpens a stone, so these factors gradually, day by day, "polish", transform our genetic status, which is either beneficial to our body or harmful to it.

The gene is no longer considered as a "closed" stationary storage system of inherited information: on the contrary, there is more and more scientific data on the plasticity of genes, their adaptive properties, the ability to react sensitively to changes in the internal and external environment of a person.
The influence of the genes that we inherit on the development of chronic diseases is only 15%, the remaining 85% is a consequence of our lifestyle.
There are six main factors that affect both the expression pattern of our genes and the genome as a whole: food, diet, physical activity, stress level, bad habits, environment (ecology). Moreover, many of these interactions of the genome and the environment are epigenetic.
Nutrigenetics is a science that originated in the USA at the beginning of this decade, studying the effect on the human genome of food, how different nutrients modify gene expression, and how this leads to a change in human health.

The right food for genesPerhaps I would not be mistaken if I called food the shortest way to our genes.

It really is. Our brain in the blink of an eye begins to produce a lot of mediators, hypothalamus – hormones, and the digestive system – a hundred or two peptidases, amylases, lipases, etc. not only during the actual meal, but long before it, when we anticipate its appearance, smell and taste in our thoughts.

Today, in developed countries, especially in the USA, a new field of scientific knowledge has become widespread – nutrigenetics, or nutrition genetics, the science of how to eat properly so that our genes are well.

Let's figure out which of the food products are now in the field of view of scientists? How do they affect the human genome? How are diseases affected?

Green tea. Perhaps everyone knows about the healing properties of the drink made from the Camellia sinensis plant. Tea, especially green tea, strengthens blood vessels and stops bleeding thanks to vitamin P, B vitamins improve overall well–being, caffeine helps us wake up in the morning, theophylline helps to warm up in the cold, and in the heat – to increase tone, theobromine stimulates the kidneys. But only in recent years, experts have begun to get closer to unraveling other properties of tea that contribute to prolonging life, general improvement and rejuvenation of the body.

In one full-scale study conducted in 1999 on more than 8 thousand people by a group of scientists from the Cancer Research Center of Saitama Prefecture, Japan, it was shown that daily consumption of green tea in the amount of 10 small Japanese cups (~50 ml) significantly reduced the risk of cancer during life in healthy people, and the use of more than five cups of breast cancer patients reduced the frequency of relapses of the disease and increased the time intervals between them. In another similar study published in 2007 in the journal Carcinogenesis, scientists from the Australian National University were able to show on more than a thousand patients with breast cancer that if you drink green tea with a frequency of about 600-700 cups per year (i.e. about two per day), then the risk of developing the disease is reduced by 50%.

How does green tea affect cancer cells? The first scientific work showing that an extract from ordinary green tea induces the death of cancer cells and blocks their division was published in 1997 by a group of American researchers led by Hasan Mukhtar. As it turned out, the anti–cancer effect of tea is due to special polyphenols - catechinins, one of the most powerful natural antioxidants. Epigallocatechin Gallate (EGCG) – the main catechinin of green tea – accounts for 50% to 80% of all tea polyphenols; a mug of green tea holds approximately 200-300 mg of EGCG. As many studies have shown, EGCG affects almost the entire spectrum of oncological diseases: from lung and breast cancer to tumors of the rectum, liver, stomach, prostate and skin.

Thus, in clinical experiments on patients with various types of cancer, it was shown that either capsules containing 200 mg of EGCG or green tea itself contributed to the recession of the disease, reduced the occurrence of new cancer foci and metastases.

How does EGCG work? According to the latest data, it can penetrate into all cells of the body, including cancer cells, where it binds not only to various proteins and proteins, but also directly to DNA and RNA, which is very important, as it shows that green tea can directly affect our DNA, and therefore genes, their correct expression and translation into proteins. It is not very clear how all this happens at the molecular and cellular level, but one thing is clear: EGCG somehow affects the expression of certain proteins, in some cases enhancing it, in others reducing it. Thus, American scientists Kathryn Kavanagh and Gail Sonenshein from Boston University have shown that EGCG inhibits the development of breast cancer in rats, and also negatively affects the growth of cancers in culture through increased expression of a special protein, p27 – a powerful natural inhibitor of cell division. In another work carried out recently at the Birla Institute of Technology, India, mice with incorporated human breast cancer cells were used – EGCG not only blocked the proliferation of cancer cells by inhibiting the cell cycle, greatly reducing the expression of genes of cell division proteins, the so-called cyclins Cyclin D, Cyclin E, CDK-4, and CDK-1, but also caused their apoptosis – complete death.

Garlic. For at least 6 thousand years, garlic has been used as a remedy with thirteen "cons" in its instructions for use: anti-inflammatory, antibacterial, antifungal, antiprotozoal, anthelmintic, antiviral, analgesic, etc. But how garlic works at the molecular genetic level, how it affects our genes, is gradually becoming clear only over the past few years of painstaking research.

What components of garlic are in the focus of attention of scientists and pharmaceutical companies today? Perhaps the most common articles include organic sulfides – diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), which are now widely used in clinical and laboratory tests around the world. Various aqueous, alcoholic or dry garlic extracts in the form of capsules, tinctures and oils are available in pharmacies. How do all these DAS, DADS and DATS work? A year ago, at the Medical University of South Carolina, USA, it was shown that in a Petri dish with human cancer cells, garlic extract induces rapid apoptosis of metastatic cells by activating the expression of the so-called stress kinases p38 MAPK, JUNK1 and cysteine proteases. Another recently discovered garlic sulfide, thiacremonone, has also proven itself as a reliable "killer" of cancer cells. It was successfully tested on metastatic cells of the human rectum at Chungbuk National University, South Korea; its effect was that it blocked such hard-to-reach genes as Bcl-2, cIAP/2, XIAP, iNOS, COX-2, aimed at the survival and growth of cancer cells, while activating pro-apoptic genes (Bax, caspse-3, PARP), designed to destroy the tumor by eliminating cancer cells.

In another study published in May of this year in the journal Gerontology, scientists from Ankara Medical University, Turkey, wondered if garlic could prolong life? After all, it is known that people who eat a lot of garlic and other spicy spices have a longer average life expectancy. Because one of the main scientific hypotheses of aging today is an increase in oxidative stress in cells with age, the byproduct of which are free radicals that destroy DNA, proteins and lipids, the researchers decided to consider those the genes that control this process. To do this, blood was tested in 13 elderly (about 70 years old) people before and after one month of garlic consumption in an amount of 0.1 g per kg of body weight per day, which is about 2-3 cloves daily. As it turned out, the scientists were absolutely right – garlic very powerfully activated the genes encoding the enzymes of the human antioxidant system (GSH-Px and SOD), suppressing the genes of oxidative, producing free radicals and superoxide enzymes, such as, for example, MDA.

Pomegranate and orange juices. The juice of the pomegranate tree Punica granatum has very strong antioxidant and anti-inflammatory properties. Recently, a group of scientists led by Hasan Mukhtar from the University of Wisconsin, USA, showed that pomegranate fruit extract also has amazing anti–cancer properties - the juice was tested on extremely aggressive human prostate cancer cells, as well as on mice in vivo (they added 0.2 percent extract to water, which approximately corresponds in concentration to pure pomegranate juice for humans). Mice that were on a pomegranate diet showed a significant decrease in prostate cancer tumors: the expression of cyclins D1, D2, E, which regulate cell division, and cyclin-dependent kinases CDK-2, CDK-4, CDK-6 was inhibited, as well as the expression of genes "harmful" to cancer cells was increased and activation was inhibited genes of "survival". To what does pomegranate juice owe such an action? As it turned out, it contains a special tannin – ellagitanin, a very strong antioxidant that can kill cancer cells and stop their spread. This antioxidant is found in pomegranate juice in a more active form than in green tea or red wine. In another study conducted at the University of California, Los Angeles in 2006 on 80 men with diagnosed prostate cancer, it was shown that drinking just one glass of this juice daily slowed cancer metastasis by four times.

Orange juice, it turns out, also has gene-protecting properties. So, recently, scientists from the University of Buffalo, USA, conducted an experiment on 32 healthy people aged 20-40 years with a normal weight, giving them four different drinks: water with 300 calories of glucose, fructose, orange juice and just water sweetened with saccharin – artificial sugar without calories. According to a blood test taken from all participants just two hours after drinking the drinks, the amount of free radicals and cellular markers of inflammation, which can potentially damage both proteins, DNA, and whole cells, was increased only in the group that drank a pure glucose drink, despite the fact that orange juice also contains glucose. Accordingly, the question arises: which juice ingredients suppressed the formation of free radicals and inflammatory processes? As it turned out, vitamin C, which is so much in orange juice and which is so famous for its antioxidant and anti–inflammatory properties, did not affect these processes, and the main "actors" were two flavonoids - hesperetin and naringenin: they blocked inflammation and peroxidation in blood cells caused by drinking drinks with glucose, up to 70%.

If you look at the whole range of products that a person eats today, then we can say with full confidence that each of them has one or another gene-regulating activity. It's just that in many cases such activity is very difficult to detect: it is either "masked" by other processes, or it requires too complex experimental schemes from scientists to somehow identify it. At the moment, about a hundred food products that have the most pronounced "gene" properties are being intensively developed in university laboratories – scientists are trying to figure out which of the ingredients of products can best "communicate" with our genes in order to create new medicines or dietary supplements based on them. Here are just a few of them (active ingredients are indicated in parentheses): grapes, red wine (resveratrol), coriander (linalol, monoterpenes), soy (genistein), basil (urzolic acid), prunes (oleanolic, urzolic acids, triterpenoids), oleander (oleandrin), red chili pepper (capsaicin), citrus fruits (quercetin), ginger (gingerol), tomatoes (lycopene), carrots (beta-carotenes), aloe (emodin), cauliflower (sulforaphane), propolis (phenethyl ester of caffeic acid, FECC), artichoke (silymarin).

What do Stone Age genes need?The fact that regular physical activity, especially professional sports, radically change not only muscle mass, but also all other systems of the human body directly or indirectly related to physical activity – bone, cardiovascular, even digestive - has been known for a long time.

But how this happens at the genome level, how it globally affects other body systems, including the brain, immune and reproductive systems, acute and chronic illness, stress, etc., gradually becomes clear only in recent years, after the complete decoding of the human genome and the invention of new molecular genetic methods of activity screening a large number of genes and proteins at the same time – DNA, RNA and protein chips.

From the stream of research papers that have flooded thousands of scientific journals over the past five years, it gradually becomes clear that any biological organism, no matter how simple or complex it may be, reacts very subtly not only to changes in internal, but also external stimuli, adapting to new conditions; and this reaction of the organism includes adaptation of already synthesized proteins and biologically active substances, such as hormones, synaptic mediators, etc., as well as changes in the genome, DNA and RNA, the expression of so-called "household" proteins and proteins, even the synthesis of new proteins that had either not been synthesized at all or were present in rudimentary quantities.

Thus, according to epidemiological screening studies, physical inactivity, which every second office worker suffers from today, increases many health–related risks: coronary artery disease by 45%, hypertension by 30%, colon cancer by 41%, breast cancer by 31%, type II diabetes by 50%, osteoporosis – by 59%, contributes to the accumulation of cholesterol, obesity, depression and increased mortality.

What happens to the modern "oblomovs in ties"? Due to lack of activity, a person loses a lot of tissues, the normal functioning of cells is disrupted. During prolonged inactivity, a lot of adaptations occur in a person: the shock volume of the heart and oxygen consumption decrease by 25%, bones lose weight 10 times faster than usual, skeletal muscles become weaker, the concentration of mitochondria decreases, insulin sensitivity decreases within three days of sitting on the couch. There is even a theory about the "genes of the Stone Age", which explains why our body begins to suffer from physical inactivity. Supposedly at the dawn of human evolution, in the Stone Age, our ancestors survived for two and a half million years due to constant physical activity, constant movement, search for new food, hunting, nomadism, etc. During this time, a huge cohort of genes appeared in our body due to selection, which "got used" to such a constant stimulus, and without it, not only muscle proteins themselves, but hundreds of other proteins involved in the energy and metabolic balance of the whole organism begin to lose activity, rhythm, and normal expression. Just today, according to scientists, this is what happens to a modern person – in our world of comfort and "couch sickness", the role of moderate but constant physical activity is minimized, which immediately affects the imbalance of Stone Age genes, which leads the body to such metabolic problems as diabetes, overweight, diseases heart and blood disorders, digestive disorders, even memory and emotions.

Scientists have long assumed that certain genes are very sensitive to exercise, but the first work that proved this appeared in 1967 and belonged to John Hollosy, who showed that rats who exercised on a treadmill for 12 weeks for two hours daily had 86% more important mitochondrial protein cytochrome-C, the electron carrier in the universal chain of utilization and energy storage in cells, than rats deprived of physical activity.

How many genes are activated in the human body under the influence of physical activity? The answer to this question was obtained in 2005 in a study by scientists from the Karolinska Institute in Stockholm, Sweden, led by Carl Sundberg. As it turned out, in healthy men, regular classes for six weeks on the most ordinary exercise bike activate such a number of different genes that are not activated by anything else – about 470. The genes of the extracellular matrix of muscle cells and calcium-binding proteins were mainly stimulated, but also important genes involved in the development of diabetes and cardiovascular diseases, and the better the result was achieved in training, the higher the gene expression was.

Today, more than 15 million Americans suffer from type II diabetes; in Russia, this figure is slightly smaller, about 5-7% of the total population, but the rate of the disease is constantly growing, the number of patients may grow to 300 million worldwide by 2025. One of the main factors leading to the development of diabetes, scientists today call inactivity. So, in one study by scientists from the University of Otago, New Zealand, which received an award at the International Conference on Nutrition in 2001 in Vienna, 79 healthy people aged 35-60 years were examined for changes in the sensitivity of body cells to insulin under the influence of physical activity (and insulin tolerance is one of the main causes of diabetes).

It has long been known that lifestyle changes have a health-improving effect on people already suffering from diabetes, but that the same thing happens in healthy people has been shown for the first time. Thus, the body's ability to use insulin for its intended purpose increased by 23% after four months of physical training (20 minutes of fitness five times a week) and a special diet. In other words, moderate physical activity led to better sensitivity of body cells to insulin, apparently due to some genomic modifications of the expression of insulin receptor proteins.

Meditation and genesToday, the practice of meditation is not the lot of lonely enlightened Buddhist monks, as it was only 50-70 years ago, but millions of ordinary people around the world.

To practice meditation is not just to feel better, to be more energetic and balanced. Meditation makes our brain work differently, the picture of brain waves changes, brain activity is synchronized, due to this, many physiological processes in the body are normalized - sleep, digestion, functioning of the cardiovascular and nervous systems, even the composition of the blood changes. From a study undertaken in 2005 by the American Heart Association, it became known that meditation prolongs life, reducing the risk of death from diseases in old age by 25%, from cardiovascular diseases – up to 30% and up to 50% – from cancer.

What does meditation do to the brain? In a study conducted in 2005 at the Massachusetts General Hospital in Boston, USA, scientists tracked what was going on in the minds of people practicing meditation using magnetic resonance imaging (MRI). Experts selected 15 people practicing meditation with different experiences (from one year to 30 years) and 15 experimental subjects who have never meditated. After analyzing a large array of information about the activity and structure of the brain, it became clear that meditation increases the thickness of some parts of the cerebral cortex involved in the processes of attention, working memory and sensory processing of information – the prefrontal cortex and the insula of the Rail.
Sara Lazar, the head of this study, commented on the results of the experiment as follows: "You train your brain during meditation, that's why it grows. After all, it is known that musicians, linguists, athletes have enlarged corresponding brain regions. The growth of the cerebral cortex is not due to the growth of neurons, but due to the proliferation of blood vessels, glial cells, astrocytes – the entire system that feeds the brain."

How little it takes to turn on the mechanisms of self-regulation in the brain through genes! As shown by experiments using MRI conducted at Boston University, USA, in 2007, just one hour of yoga is enough – and the brain begins to produce 30% more of such an important inhibitory mediator as GABA. A decrease in GABA in the brain is observed in depression, chronic states of fear and anxiety, as well as epilepsy. Thus, practicing the most ordinary yoga could replace drug therapy here.

Meditation not only relieves stress, fatigue and anxiety, but also rejuvenates the brain. So in the work done last year at Emory University, USA, 13 people were studied practicing Zen meditation, which is used by Buddhists in Japan, China, Korea and Vietnam. The work was the first to show that meditation can reverse the aging process. It is known that with age, the cerebral cortex decreases in thickness and volume, it seems to shrink, loses water, trophic worsens, attention and memory fade, speech slows down. So, meditation stops these processes – all Zen meditation practitioners in adulthood or old age did not have age-related changes in the cortex, and also demonstrated normal performance in attention tests.

If meditation can have such a strong effect on brain morphology, then it means that there are modifications in gene expression. In the work of researchers from the All India Institute of Medical Sciences, New Delhi, India, published in February this year, the results of blood tests of 42 people who have been practicing the Sudarshan Kriya breathing technique for at least a year, when a person breathes in different rhythms, were given. The results of gene screening showed that those who practiced meditation had a higher level of expression of such important genes as genes regulating antioxidant stress, immune response, and genes regulating apoptosis and cell survival.

I will give another example of the impact of non-traditional health practices on the regulation of the genome. In 2005, scientists from the University of Texas, led by Quan-Zhen Li, tested blood cells - neutrophils using DNA chips, in six Asians who practice at least a year for 1-2 hours a day a special meditation technique of ancient Chinese qigong. The result was impressive – all of them had strongly activated genes that strengthen the immune system, reduce cellular metabolism, and accelerate the healing of any inflammatory processes, wounds. More than 12 thousand genes were scanned, 250 of them were changed, 132 were suppressed, 118 were activated. The most powerful changes were made by genes from the ubiquitin-dependent protein elimination system, which is involved in the etiology of many diseases, such as cancer, diabetes, high blood pressure, sepsis, autoimmune diseases, inflammation, and diseases associated with aging. Many enzymes of this system, including ubiquitin itself, were suppressed in practitioners of this technique. The expression of 10 genes from 11 so-called ribosomal proteins involved in protein synthesis was also reduced. Immune response genes, interferon, as well as genes encoding antibacterial and antiviral peptides, Defensin-3 and cytokines, were on the contrary enhanced. Interestingly, reducing calorie intake is the only method to date that extends the life of rats, mice and primates, also reduces metabolism and inhibits ubiquitin, the protein elimination system in all cells.

Fasting changes everythingThere are many different modern methods of fasting – according to Bregg, Shelton, Malakhov, Voitovich, dry, full, on juices, vegetables, etc. – although the phenomenon of fasting originated at the dawn of mankind.

Our ancestors understood its importance for the physical and spiritual health of a person so much that fasting has long been used not only in alternative medicine of all peoples, but also in the ordinary way of life of entire countries, and in order for the healing effect for the body and soul to be even greater and have a "national" scale, various fasting practices have been integrated into religions traditions, culture and art – Lent for Christians, Yom Kippur for Jews, Ramadan for Muslims, yoga for Hindus, eight presepts (rules of conduct) and Pratimoksha for Buddhists.

Today, there is only one scientifically proven method of extending the lifespan of both animals and humans – reducing calorie intake, when the diet provides all the necessary nutrients, vitamins and minerals for a healthy and fulfilling life, but has a reduced amount of energy (calories) contained in the products. Such gentle fasting, as it turned out, pushes back or completely blocks various pathological changes associated with aging, and increases life expectancy from 30% to 50% in many animals – from fish and spiders to rodents.

Back in 1934, scientists from Cornell University Clive McCay (Clive McCay) and Mary Crowell (Mary Crowell), using laboratory rats, as well as Roy Walford (Roy Walford) from the University of California, a participant in the project "Spheres-2" and a pioneer of a whole scientific direction in gerontology, in the 1980s, conducting experiments on mice have shown that gentle fasting (cutting the consumption of calories per day by 25-50%) not only lengthens the life of rodents by half, but also makes them physically and socially more active. Another researcher, Morris Ross, conducted an experiment on rats, dividing them into three groups in which animals consumed different amounts (10, 25, 40%) of proteins per day, and a group that ate without restrictions. This study showed that rats who did not deny themselves anything matured faster, reached puberty at an earlier age and had more offspring, but died earlier and suffered from cancer and other diseases more often than rats "on a diet". Roy Walford commented on this in an interview with Life Extension Magazine: "... it seems that we are programmed by natural selection to choose such a diet in order to reach puberty as quickly as possible and produce offspring as much as possible and earlier – this is good for the survival and evolution of the species, but it is a complete disaster for the survival of the individual".

Which genes are changed by sparing fasting or cutting calorie intake? Scientists from the University of Wisconsin, USA, using DNA microchips and scanning 6347 genes in the cerebral cortex and cerebellum of laboratory mice, found that old mice had overestimated the expression parameters of more than 120 inflammatory response and oxidative stress genes, which suggests that microinflammatory processes are constantly going on in the "old" brain, according toapparently, due to damage caused by free radicals generated by oxidative stress. So, in mice whose daily calorie intake was reduced by 25%, all these genes were normalized.

In another experiment conducted in 2007 by scientists from the Pennington Center for Biomedical Research, USA, 36 healthy but overweight young people were tested, dividing them into three groups: the control group received 100% of the required amount of energy in food, the other two were calorie-restricted for six months – one received 25% less than the "norm", the other – 12.5%, but combined diet with exercise. As shown by the genetic analysis of muscle tissue taken from all participants after the experiment in the form of small biopsies, both groups "on a diet" increased the number of mitochondria and reduced the amount of DNA damaged by free radicals in cells. Scientists also found that the "diet" served as a powerful stimulus for activating the expression of many genes (PPARGC1A, TFAM, eNOS, PARL) encoding important functional proteins of our energy cell stations – mitochondria. Interestingly, such a diet also activated a special gene – SIRT1, the human analogue of the Sir2 gene found in yeast, nematodes and fruit flies, the activation of which leads to a longer life due to improved cellular metabolism. A similar study was conducted by a group of scientists from Harvard Medical School and the National Institutes of Health, USA, and published in the journal Cell in 2007. The researchers found two more genes from the same family of mitochondrial sirtuin genes - SIRT3 and SIRT4, which reacted to calorie reduction by activating through a chain of reactions of other important NAMPT and NAD genes. All this led to the fact that mitochondria became stronger and healthier, produced more energy, due to this, the aging processes of cells were greatly slowed down, a special "suicidal" program of cell self-destruction was also inhibited. Interestingly, approximately the same thing – activation and optimization of mitochondria – occurs at the molecular level after physical exercise.

According to the latest data obtained in a number of studies, it is enough to comply with the following requirements – and the risk of developing diseases such as colon and lung cancer, myocardial infarction, stroke, type II diabetes, obesity and many others can be reduced by 70-90%:

• physical activity equivalent to 30 min. and more brisk walking;
• at least 100 micrograms of folic acid per day;
• less than three glasses of weak wine a day;
• no tobacco during life;
• less than three meals a week, the menu of which includes red meat;
• reduced intake of saturated, trans fats and sugars;
• sufficient intake of polyunsaturated fats, omega-3 fats and dietary fiber from cereals, more greens, vegetables and fruits.
• You just need to fulfill this set of very simple requirements – and your genes will be happy!

•  Nutritional Genomics: Impact on Health and Disease. By Regina Brigelius-Floho, Hans-Georg Joost, Wiley-VCH, 2006.
•  Nutritional Genomics: Discovering the Path to Personalized Nutrition. By Jim Kaput, Raymond L. Rodriguez. Wiley-Interscience, 2006.
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•  Nutrition and Fitness: Diet, Genes, Physical Activity and Health. By Artemis P. Simopoulos, Konstantinos N. Pavlou. Karger Publishers, 2001.
•  Nutritional Genomics – A Consumer's Guide to How Your Genes and Ancestry Respond to Food: Tailoring What You Eat to Your DNA. By Anne Hart. iUniverse, 2003.
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Oleg Senkov is a neurophysiologist, received bachelor's and master's degrees from St. Petersburg State University, defended his doctoral thesis at the University of Hamburg (Germany), currently a researcher at the Institute of Neurophysiology and Pathophysiology of the University Clinic Eppendorf in Hamburg. His research interests include the study of the brain, in particular, the basics of memory and learning at the molecular genetic, cellular and systemic levels. Hobbies: journalism, photography and web design. Home page: http://www.olegsenkov.com/Portal "Eternal youth" www.vechnayamolodost.ru


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