The extension of the path of life, resveratrol, etc. and the fight against cancer: dual mitochondrial biogenesis, the mechanism of metabolism and applications practices
The Way of Life Extension, Resveratrol, etc and the fight against cancer: the dual mitochondrial biogenesis, the mechanism of metabolism and practical applications.
Gregory S. Bambeck Ph.D. Michael Wolfson, JD, MBA
Kent, Ohio 44240
SUMMARY STATEMENT: cancer, heart disease and diabetes type II, three more victims of the first and the second nation in the world of humans (85%), and illness of the opposition jet Health source of youth, are ultimately defined the framework for a global singular unifying hypothesis. Experimental molecular mapping shows that mechanisms that regulate the process of defining a real and true clinically demonstrated for the first time. Provision of public health practice and the possible blocking and implementation of life extension are easily accessible to all. There are three sections: abstract Thus mechanisms, practical applications. Happy reading!
ABSTRACT
Complete mitochondrial biogenesis is a time of two phases consisting of a first phase mainly involved in replication anabolism cell, and performing more than a thousand a constituent of mitochondrial proteins that create new, but mitochondrial NADH OX PHOS inefficient. These replication events, homeostatic control cell to regulate a late stage of respiratory chain proteins that create effective mitochondrial NADH OX PHOS associated with a shift toward catabolism and autophagy of dysfunctional mitochondria and other cellular debris. First phase (neogenesis) supports cell growth, rejuvenation and vitality throughout the body in the short term, whereas the late phase (ReGenesis) is compatible with the maintenance cleaning and repair of cellular functions of life extends to long term. The fair efector at the entrance of mitochondrial biogenesis mitochondrial proliferator coactivator (PGC 1alpha,). Their standards institutes neogenesis and its regulation by ReGenesis institutions. Restriction calories (RC) to regulate the active kinase adenosine monophosphate activated ReGenesis (AMPK), while cancer active neogenesis in the absence of regulation ReGenesis down the path of AMPK upstream of PGC-1alpha. Latest "rediscovered" show that the metabolism of cancer cells a proposal in 1980, is correct in its unique metabolism. Most cancer cells are addicted to the glycolytic enzyme fetal mutation was sugar, "supported by the inefficiency of mitochondrial ATP production requires. Cancer cells are stuck in this state drive cellular growth (metabotype), and harden replicative under the influence of mitogens. Recent discoveries show that inhibition of real-life road extends CR supports sugar junkie, this "state of growth through the creation and maintenance of the inefficiency and neoformed mitochondria in the presence of forced hyperglycolysis. The blockade of glycolysis in the fetus and restore the model RC creates the path of mitochondria ReGenesis and effectively stop cancer cell growth, and sometimes even initiate apoptosis of cancer cells. We describe mechanism of the track as a one-way feedback loop starting with the objective of the RC, AMPK, and how it regulates mitochondrial biogenesis, the reactive species oxygen (ROS) output, which feeds back to the AMPK. Also the effect of resveratrol CR mimetic, and its bioavailability in this context, and use of these agreements to explore synergies simple lifestyle and nutraceutical products for cancer, the main diseases of aging, and even the same age.
FEED MECHANISMS
To make it easy to understand, start with the rules of the road. First, when we use the adjective 'chronic prefixes "or" hypo "or" hyper ", we refer to aberrant against nature or human-caused impacts on normal homeostatic systems or typical passages in the standard Insect physiological metabolic systems. These words are used to highlight a strong main effect or whatever. Secondly, since CR is the gold standard aging, we will use as a base "A" or reference point that most of our raids to leave, then return. Third, we will focus mainly on bike paths toggle switch to multiple AMPK Review of rapamycin (TOR) for PGC-1alpha Sestrini ROS (SESNA) and re-AMPK with regulations rather than the regulation of AMPK indeed all other components of the cycle thereafter. Because the system is a closed circuit everything is above all the rest well below the rest, like a snake eating its tail proverbial. However, extrinsic factors that affect any of the components can be mounted in the immediate upstream regulators, as is often the point. Memory, or keep a notebook with this simple AMPK, TOR, PGC-1alpha, ROS, circuit Sesno, main reference point, the discussion is based.
We begin with a brief overview of the path CR. Most simply, CR activates AMPK, which regulates TOR. Down regulate cellular metabolism moves Tor anabolism and catabolism, clearing debris begins cell autophagy, such as dysfunctional mitochondria and regulates PGC-1alpha. When regulated PGC-1alpha results in ReGenesis existing mitochondria by opening the transcription of mitochondrial proteins of the respiratory chain effective link between the production of NADH ATP OX / PHOS. This makes mitochondrial ROS production in the fall, which in turn, regulated by SESNA ROS sensor. SESNA then down regulates the stimulation of AMPK, which makes the circuit to rebalance back to your center of homeostatic. Note here that AMPK regulates active and stay SESNA dormant until activated SESNA not, so their solution is activated so that its solution is passive Down. Thus, following RCA bypass and chronic AMPK SESNA continuously regular CR improve the way in reducing mitochondrial ROS. Elevated ROS is the main shorten the life of system components, and therefore, repression is the highest dilution single life, called. This example shows that increasing AMPK activity leads to a decrease in the four (RPT, PGC-1alpha, ROS, SESNA) elements in the circuit unidirectional feedback. By contrast, the decrease in AMPK activity, as in cancer cells p53 dysfunction, causes up regulation the same four elements downstream of it, which, moreover, the causes of inefficient mitochondrial neogenesis.
As illustrated in our RC model, the TOR AMPK in PGC-1alpha are key inputs and responses mitochondrial biogenesis, whereas ROS are the main results SESNA mitochondria and their answers. We know that there are many steps between each of these five large rocker switches and there are many branching paths and up and down genes and regulations under the switch each switch but are mentioned in passing that if necessary, because it is the center ring is essential for unidirectional cancer, diseases of old age and aging reduced metabolism affects us here. elegant extension and evolution of this trend and basic circuits and channels relating to the detection of nutrients may be in Science, vol.327, vol.328 p.1210 and 05/03/2010, 16/03/2010 P. 324. Finally, the paper focuses on cellular bioenergetics and metabolism, because these features back to hail eukaryotes and finally won his place in the cancer cell about desktop systems with telomeres, growth, apoptosis, etc. Later, we'll see how AMPK, TOR, PGC-1alpha, ROS, SESNA circuit is exactly the same circuit to combat cancer and the extent, but are active in the opposite direction. We will see that "cancer cure" or at least control, and share the RC circuit in exactly the same operations in the same direction, Trained hyperglycolysis mutational with being the only cancer, but critics highlighted. But look in the first place, every major component of the system.
AMPK is upstream of the CR way. AMPK control cell energy charge is sensitive to the AMP / ATP, which generally represents the availability of nutrients fuel elements the cell. High levels of the ATP molecule represent energy-rich nutrient adequacy and low fuel Concomitant GPA. By contrast, high and ATP low AMP indicate the availability of fuel in low as in CR, which governs through AMPK to AMPK kinase. Increased AMPK may inhibit TOR countermanded by the means of factor of growth that activates the TOR. Things that activate AMPK inhibits the TOR, and things that prevent AMPK allowed TOR. Things that activate AMPK and pave the way support extending CR metabotype and prevent cancer. Located just upstream of AMPK, active SESNA car when AMPK is activated by suppressing cancer cell growth (p53), or ROS, the majority of mitochondrial origin. The p53 protein is pro-apoptotic and inhibition or malfunction was found in about half of all cancers. The components or systems that reduce the activity of AMPK reduced the life expectancy and promote cancer metabotype. CR mimetics prolong life expectancy and prevent metabotype cancer.
The latter effect is illustrated by the antiretroviral drug, type II diabetes, metformin, which is a direct activator of AMPK, causing the reduction of insulin resistance typical CR and TOR inhibition of downstream. Metformin has been found to increase the life expectancy of cancer victims, diabetic and healthy animals. direct activation of AMPK by metformin enhances ROS SESNA enabled switch or manageable and the inactivation of p53 SESNA defective. concentrations intracellular resveratrol in the group of 20-50 um to activate AMPK even with metformin. resveratrol concentrations of free food rarely reached above the low single digits UM. Metformin is the best known example of a chemical that mimics CR.
Now, let's take a brief tour of Tor. In our model one-way circular metabolic activity, Tor is the first major downstream target of AMPK. Tor is an important NADH / NAD redox sensor switch and a master metabolic regulator involved in a dizzying array of integrated channels, is in a web search on "Target of rapamycin in mammals. Fortunately, affecting several major roads converged and divergent on the TOR and exit, allowing us to simplify things. For example, mitogens, growth factors, hormones, and act in terms of reference through a common TSC2 AMPK called intermediate. Thus, in a functional sense Simplified, terms of reference reflects a delicate balance of the AMP / ATP energy charge, NADH / NAD redox state, the availability of nutritious fuel elements, mitogens, growth factors, growth factor suppress the ROE and genotoxic load. digital outputs that are multifunctional inputs, but are most often associated with integrated control systems that are mutually exclusive anabolic or catabolic.
The regulation of terms of reference for the high AMPK activity (CR, for example) makes a move toward efficiency catabolic to support the implementation of caloric restriction for maximum fuel economy energy fuel element maximum possible nutrient limiting conditions. In this scheme, other TOR way institutes increased mitochondrial respiratory efficiency through ReGenesis, and yet another way TOR regulates the autophagic cell debris and mitochondria dysfunctional. the cell disruption efficiency, reduction of ROS and increases great hope life support functions and promote metabotype cancer. This process also can be done by the TOR inhibitor suppressor and foreign tissue rejection, rapamycin. The rapamycin may facilitate the extension of life by pulling one end around the TOR and direct inhibition of AMPK to change the disk status of cellular anabolism to catabolism, and also very important to boost the status of the mitochondrion in regenic efficiency by regulating PGC-1alpha.
Finally, the last component in the side of the mitochondrial biogenesis of the loop unidirectional, a brief summary of the role of PGC-1alpha might be in order. When PGC-1alpha is activated, it becomes more than a thousand genes that are involved in mega-function very complex, but the singular to build more mitochondria (neogenesis). As we have seen, when Tor is regulated in turn to regulate PGC-1alpha and construction of all mitochondria, except respiratory chain is established. The elements of the transcript of the respiratory chain can be constructed when PGC-1alpha is regulated, more later. chronic stimulation of PGC-1alpha regulation by Tor chronic growth hormone in a continuous state of mitochondria neogenesis ReGenesis with the poor, which is a high ROS generator.
This is nothing more evident than in metabtype cancer cells. When mitochondrial respiratory NADH OX / link PHOS is compromised by neogenesis without mitochondria ReGenesis, but mostly catabolic function, glycolysis actually enhance support for increased anabolism and, consequently, alter the balance of the products of glycolysis, mitochondrial NADH raw materials and reduce power to the construction of cells, all backed by an increase of glycolysis the ratio of mitochondrial ATP production. In his thesis, Kent State University in the mitochondrial changes in transplanted mice lymphoblastic lymphoma DBA/1J in 1980, examined dozens of Bambeck type of cancer cell mitochondria, and saw a model. He offered a detailed picture of cell nutrients and catabolic NADH pattern general building blocks and a detailed narrative description of these connections. AMPK, TOR, C side of the PG-1alpha mitochondrial entry of the Czech Republic, only now available, and concludes with the controls to test their hypothesis, we have barely begun to rediscover the past two years. It's amazing accuracy This year thirty above description is given there was no awareness of AMPK, PGC-1alpha digital and the wide range of intermediate connections in the way of regulation, at that time. But today, our new knowledge back yet established for the control of oxidation-reduction, responsible for energy and metabolites which could be followed, even at this time, in the absence of this knowledge modern regulation. This was done by constructing diagrams of metabolic fluxes in different drive states and deduce where the links of control must exist, though not yet known.
As metformin can pass High SESNA directly instead AMPK regulation and rapamycin can be circumvented by direct regulation of AMPK TOR T3 thyroxine in the form of non-shivering thermogenesis, most Tor can avoid regulating PGC-1alpha. In addition to ignoring the mandate anabolic / catabolic Rocker, which can help illustrate the temporal duality of the role of PGC-1alpha.
A single dose of thyroxine binds to DNA by T3 nuclear and mitochondrial biogenesis master control activator PGC-1alpha co activator binding and transcription begins. In five hours, which activates PGC-1alpha causes more than 1,000 nuclear genes that are specific to the construction of the new poor mitochondrial respiration to start transcription. These very long mRNA that contains the code for their respective products of genes and the sequences that lead their respective targets mitochondria. These mRNAs are exported from the nucleus into the cytoplasm to form polysomes translational outer mitochondrial membrane, where it joins the endoplasmic reticulum. Depending on your signal sequences, protein mitochondria are transported to their home residence mitochondrial functional compartments. After about 48 hours, thyroxine and decreases PGC-1alpha signaling system and a set of late nuclear and mitochondrial genes specifying components of the respiratory chain is activated, the origin of these newly formed together to become bad mitochondria in mitochondria that produce ATP efficiently regenic. In chronic hyperthyroidism, the newly formed phase is highly regulated and its place in relation to the phase of ROS and damage regenic severe enough to substantially reduce life. A common term for the early termination of hyperthyroidism is the "wear" because, Unlike Tor neogenesis and anabolic function activated, the activation is tyrosine catabolic.
In the phase of tyrosine regenerated activated There is also a set of uncoupling proteins (UCP), which are products that allow protons NADH to 'leakback "in the mitochondrial matrix chemiosmotic potential without being captured and stored as chemical energy of ATP released. Although this simplified description, the net result is that energy collection takes the form of heat, it is easy to measure. Thyroxine also proposed that the catabolism fuel sources of energy with low carbon percentage of sugar by lipids high-energy carbon, and where appropriate, of the protein. However, when PGC-1alpha is regulated by the TOR, anabolism is compatible and glucose is the preferred fuel. This difference is not only important, but very amplified when one considers that cancer metabotype later. Regulation of PGC-1alpha chronic if stimulation motor anabolically of growth hormone or catabolically driven digital direct stimulation of thyroxine as in hyperthyroidism, the results Mitochondrial biogenesis incomplete ROS trapped in a newly formed state of output high enough to cause cancer and shorten life through ROS produced genotoxicity and randomized Stochastic protein aggravated by the absence of phagocytic functions Home maintenance and DNA repair systems. neogenesis in the absence of chronic ReGenesis not only is an inducer of cancer cells metabotype, but an officer metabotype cell cancer, too.
Another way to decouple mitochondrial ATP production of NADH in the cytoplasm Export NADH through NADH / NAD system shuttles. Growing and dividing cells, the redox and the load Power still has lag, if this system is a little harder. In addition, no cell division of rest in excess of requirements citrate Krebs cycle may inhibit the "commitment" phospho-fructo kinase enzyme (KFC) at the source of glycolysis. Fetal KFC is elevated in cancer cells. Although is an inefficient producer ATP and NADH, glycolysis can be activated rapidly when stimulated explosives. For the sake of brevity, we will not distinguish between the two forms of dissociation in this document.
AMPK described above for the PGC-1alpha TOR Part of the inputs are one-way closed circuit system ReGenesis mitochondrial neogenesis /. The ERO SESNA part represents the feedback loop output VSWR AMPK. Although the exact mechanism of mitochondrial ROS production SESNA must be interconnected, as it passes required and the net results are unequivocal. Increased ROS ultimately leads to activation of Sesno, which in turn activate AMPK to inhibit TOR by controlling PGC-1alpha establish ReGenesis reduce mitochondrial ROS. SESNA Drosophila gene knockout die early age-related disorders, and antioxidant vitamin E protects life civil-length in the germ line, SESNA.
The system, as described so far is more clarification to extend the life which belongs the generation and maintenance of cancer metabotype, soon to be discussed. Basically, the extension through upregulation of AMPK occurs CR, mainly due to the reduction of ROS ReGenesis caused by mitochondrial ATP production of mitochondria effective. Basically, this puts the adult body in a pattern extended to standby power supply of nutrients can support fertility and other features of energy-intensive such as immune surveillance, wound healing injuries and muscle strengthening.
Here's how the resveratrol probably fits in the picture. In quantities of food, free resveratrol enters the interstitial cells in an amount too small to mimic caloric restriction in a modest degree. In such quantities, which regulates mitochondrial ReGenesis neogenesis more than a moderate but significant adjustment of thyroxine. Presumed mechanism for its imitation of activation of beta-estradiol stimulation of thyroxine hypothalamic releasing hormone stimulating hormone. However, resveratrol is also a powerful anti-oxidant. In this interaction, which acts as a constraint mimetic goal in calories rather than a real boost AMPK agonist. What is not significant to regulate AMPK, PGC-1alpha, but active, but regulates the TOR, therefore, not act as growth hormone of any kind. It is a huge difference, because as the elevation of the AMPK CR, certainly not anabolic Sports and its own influence catabolic. Moreover, unlike thyroxine stimulation is that it captures the ROS, suggesting a ReGenesis neogenesis as a result, another net result of RC. Regardless, resveratrol is only neoformed regenic in these quantities. Mixed How is the CR mimetic function plays in this scenario tortuous is the author of the individual and their impact on the ROE digital load is unknown. Most evidence supporting this scenario is that the murder of a resveratrol dietary cancer and functions life extension, as seen in vitro at concentrations ten times are not significantly manifest. In terms of food, it would be wise to force ReGenesis neoformed a defect to cover the bet only CR to an end as a result. endurance exercise after a vigorous pace in the night would become probably around the creation of an oxygen debt sugar exhaustion. In humans, resveratrol followed by a year, even without fast-twitch becomes fast glycolytic white muscle fibers aerobic slow twitch red, and the cell volume increased mitochondrial about5% to 30%, with characteristics regenic. Similar results were produced in the fast runners in the absence of resveratrol. The experiences we need are fairly obvious.
The extension of life and cancer in vitro apoptotic effects of resveratrol in the range of 20-50 uM are so attractive that this difference should bioavailability of food be resolved soon. Already, the resveratrol-free serum well above the target range of 20-50 uM reportedly industrially. Furthermore, synergistic molecules, such as quercetin and Coenzyme Q with antioxidants in the mixture. However, the regulation of the TOR and mitochondrial ReGenesis are required for the full impact of CR. We explore these issues in practical applications later. But for now, our attention metabolic feedback loop attention on metabotype cancer.
From a genetic perspective, cancer cells seem crazy. Among chromosomal inversions, insertions and unequal cell divisions that cells done in a heterogeneous mix hundreds of thousands of genes in the haploid or polyploidy, add to that, the modified protein supplement and losing his post translational modifications, and the result is a bewildering number of changes of any data that is not fully differentiated cancer progenitor cells. Although each type of cancer cells retain many features of this type of stem cell, the analysis of the pistol as 2D electrophoresis and tryptic digestion multi-gradient HPLC (chromatography high pressure liquid) and MALDI-TOF (matrix-assisted laser desorption ionization time of flight) mass spectrometry to show that no two cancers are equal and that a given cancer is not even himself. A cancerous tumor looks like Theme is a heterogeneous type of precursor cells committed to a hyper-Darwinian selection for survival in an organization trying desperately but if not, to kill him.
Fortunately, cells cancer, must obey the same laws of thermodynamics, and must be made within the toolbox of the metabolism of sugars, amino acids, lipids and nucleotides distributions and redox (NADH / NAD) and the power companies (AMP / ADP / ATP) that allow the cell to grow and divide, in order to be able to grow and divide, and so on. Note here that sugar and carbohydrates are the cheapest source of energy in the food web of biotic earth. Lipid is a bit expensive, but proteins and nucleotides are very expensive, because nitrogen and phosphorus are nutrients limiting redox, almost everyone. So Sugar is the preferred fuel for growth and cell division (especially in hypoxia), while lipids, proteins and nucleotides are kept as building materials. The limitations of nutritional and metabolic requirements have been set in stone billion years before multicellular organism there first. In addition, cancer cells have many features with fetal cells. Very Importantly, they are still behind their fuel supply and the necessary oxygen, so they take a blood vessel metabotype induces hypoxia develop. The growth of blood vessels is called angiogenesis. They also increase their glycolytic rates dramatically, in some cases over 1000%. The most important of all, will the relationship between glycolytic ATP production mitochondrial although a higher percentage due to the lack of mitochondrial and / or ineffectiveness. Because fetal cells, they become addicts of glucose to infect the liver the production sugar gluconeogenesis process of their host, but unlike fetal cells, they can not shut down glycolysis.
A cause of tumor hypoxia and needs of cancer cell growth regenic neogenically fractures, rate of its function. Many books have been and will writing on the fetus and the environment and its development and implications of bioenergy organismal culture conditions, and especially now, especially the main elements the trajectory of community radio stations have been clarified, and the participation of cancer and other diseases of aging. But for now, the main points described above shall be sufficient.
How did all this based CR AMPK controls a feedback loop to get in shape in metabolism of cancer cells is through a wonder and an amazing achievement surprising news. Laudits attach great heaps of praise for the scientists who have Slogger through years and hundreds of thousands if not millions of hours of work to clarify details of the loop and its large number of auxiliary lanes. Even cancer research but the authors and CR (as well as diabetes and cardiovascular researchers) may not know, their results show that cancer and the Czech Republic are exactly how metabotype in the same way, but operating in opposite directions and essentially different conditions, with the loop of AMPK and mitochondrial neogenesis ReGenesis vs control elements based on the two cases, and glycolysis of cancer cells provide their own opposition. The fact that type II diabetes and cardiovascular hyperplasia and hypertrophy heart are also the results of this model is even more surprising. Readers of this document would be easy to understand and be pleasantly surprised by connecting basic cancer if they read (and this is a must read), New Scientist, 15.5.2010 p.6, a brief overview of what is lower, after correction Discussion Warburg.
In the last two years, cancer researchers have shown that any indication of the metabolism and glycolysis aerobic cancer cells are particularly described above in 1980. In that time, assuming fixed a bug in the Warburg hypothesis aerobic glycolysis, postulating that the mitochondria of cancer cells that suffer a deficit of ATP production resulting in aerobic versus anaerobic ATP Warburg differential concept deficit of mitochondrial oxygen consumption. It is an important distinction, because it alters the NADH / NAD, ATP / ADP and substrate flows into the cell. It has also been described in detail how this deficit has been incorporated into the activation of the enzymes of glycolysis fetus force the system to complete a previously unknown, the system anabolic operating control an irreversible state of cell growth and division, we have invented metabotype cancer. Interesting methods of attack to kill or renormalizing cancer cells have been considered at the time. With our new knowledge, we may want to reconsider some of these strategies in the search for synergies. It is very casual how the "rediscovery" of the system password during the last two years is also the same in a wide range of indications. In all cases, whether old discovered, rediscovered or new findings, the results unambiguously show that cancer is mandatory metabotype and inextricably linked to the process CR, and greater mitochondrial neogenesis with a bit of ReGenesis. This is the synthesis that is quite remarkable news.
As an overview of metabolic point of view, most cancer cells are trapped in the fetal enzyme mutational up-regulated glycolysis induced sustained hyper-regulated AMPK deficiency leads Tor etc regenerated mitochondrial ATP production, so that the cell can not recover, as it can in the cells of fetuses, at least normal circumstances in vivo, the short answer artificial. Under the influence of drivers increased or decreased mitogen or growth suppressor cells dysfunctional Cell rounds is forced to uncontrollable growth and division irreversible. Metastasis and ignore other issues here that we focus on the old drive metabolic states induction and maintenance of cancer cells, unlike progression.
What researchers in article New scientific review has found that blocking glycolysis pyruvate kinase leads fetus dichloroacetate "awakened" (words) gene ReGenesis (our words), restoration of normal glycolysis to mitochondrial ATP production and the ratio of metabolites of the current, and given the growth cancer cell in a virtual paralysis in the brain glioblastoma. In addition, hospital records showed that the previous rules in place of AMPK with metformin in diabetic patients are victims of lung cancer has increased the survival time. This is the first time in humans, that is proof that CR and therapies cancer share the same exact AMPK control circuit, and an anti-diabetes, to boot. We also have Note that the system has been proven to work in many cancers of mice, and this is a moment of Cancer Research mice and humans share actually an old road and a challenge metabolic control. This is just the beginning "mass" phase of the work of man. More sophisticated attacks are planned in the hope excited. Hopefully we do not find many enzymes blockers also fetus, since until thirty years ago, knew that other enzymes of the fetus that support changes in glycolysis and phosphate anabolic agent NADPH supply pentose shunt in several types of cancer.
Reduce hyperglycolysis and efficiency are two key mitochondrial effect of age-related slowing as cancer, type II diabetes and cardiovascular disease. For example, aging adult cardiovascular disease institutes ROS damage and mitogens in hyperplastic intimal thickening of the vascular tree, ventricular hypertrophy concomitant with the decrease of mitochondria and a change in the steady state efficiency of lipid catabolism of high energy glucose catabolism low efficiency. Compare this with the hypoxic fetus, if the birth abundant supply of oxygen full lung followed by heart mitochondrial biogenesis, a rapid change in the catabolism of carbohydrates, conversion high lipid affinity for fetal hemoglobin F free-living adult parasites lower affinity of hemoglobin A and a decrease in the production of ROS. The first is a interim measure to respond to ROS-induced genetic alterations, while the second is a finely tuned gene in the response of the energy system. Both are AMPK mediated by digital feedback loop, etc., and adequate stimulation of the loop through CR or its agonists are shown to make a significant impact on these forms of inhibition decreased cardiovascular accurate. Diabetes type II is a similar body set of answers to the same class if the insults in the disintegration cardiovascular, and can be avoided by activating AMPK directly metformin reduces insulin resistance and creates home and cellular mitochondrial ReGenesis. Metformin has been in use since long before they were even unaware of such things as the feedback loop Sestrini mitochondrial neogenesis ReGenesis and its relationship to hyperglycolysis fetal!
Neogenesis and ReGenesis Both are essential to maintaining the state of young children in adult cells. By analogy, it's like neogenesis a construction team that built a new house, but leaves a disaster-related construction waste. Regenesis is like cleaning and maintenance monitoring makes the house into a home habitable. In adults, aging cells do not divide, the two functions are altered ReGenesis is poorer, as the aging of cells tend to move toward ruin hyperplasia mounted. The decline in growth hormone and steroids inhibit androgynous features and newly ROS formed rejuvenating exacerbates the duties "in the process the abundant nutrition oxide and inhibits the functions regenic. This may explain why CR seems to have an effect virtually zero if started before the beginning of the Middle Ages. This could also explain how chronic neogenesis, such as growth hormone, profitability short term with long-term "burnout." On the contrary, may explain how chronic ReGenesis, with the RC, the performance of long-term gains, but with serious quality problems. Neogenesis may periodically with a defect ReGenesis fast since it is much more typical of young cells, can provide optimum results.
A review of these mechanisms has left these two authors breath when considering the scope of its medical implications, both in terms of monetary cost of medical savings, and in terms of the impressive number of years the quality of life of the man who could be added to total. It is cool how the main elements of the three biggest murderers of the human race with a fountain jet Health of youth, all are part of a unifying hypothesis unique and global. Therefore, everything has been done in that document is defined in the system.
PRACTICAL APPLICATIONS: THE FUTURE Minnesota
It can be seen as a wild-taking material, but on the basis of the foregoing, the proposals could actually be stronger than a lot of things that peppers Cash grocery posts. However, remind everyone that we are not doctors and therefore not allowed to practice medicine. It is not our intention. Any use of the information contained therein is up to the reader. We expressly disclaim any liability arising directly or indirectly from the use or application of any information contained in any of these items. As what I write here is more of a free flow of speculative ideas to participate in phytonutrients and cons of lifestyle choices.
Recent longitudinal studies show that food is killing us more firmly sugar that is the content protein or high saturated fat, found in animal products. Diseases of aging such as diabetes, heart disease and cancer, killing the vast majority us and the surplus food (extracellular) sugar is a major and more and more guilty. However, be careful before AMPK, TOR, PGC-1alpha, ROS SESNA cycle yields the decomposition of the system clock to the diseases of aging, despite dietary sugar, as metabolic changes intracellular time. In other words, even if the sugar led to the creation of our life, from beginning to birth, over time will kill us, but not eat. This is "natural" aging, and the data clearly show that abnormal tension or supernatural must be done to get the non-natural or supra-natural condition known as prolongation of life beyond natural limits or expected. Let's face caloric restriction (CR) is drastic and natural in the sense that, in nature, we sometimes lack food. No organization exists "naturally" is CR presence of adequate food. Mega doses anti-oxidants or a hundred bottles of wine from the daily value of resveratrol is decidedly unnatural.
Who said, these things have been found to undergo the test of time. For example, the Chinese have been drinking a high knotweed root extract resveratrol call itadoli for millennia without beneficial results and claimed known side effects, except for some occasional intestinal discomfort are mainly due to the emodin, a joint statement, which also mixtures is not modern. The remainder of this brief analysis is of course primarily devoted to some "natural" things people could do without having to live with a menagerie more support in the life of anorexia in close collaboration with its attendant obstacles to the muscles, healing, immunity function, fertility and others. The focus here will be in force a default state of the mitochondrial ReGenesis, which is at the heart and soul of aging and inhibition of induction cancer cells and maintenance. Therefore, the discussion is completely avoided admonitions school teacher and used as "eat your vegetables", "Take your vitamins "," regular exercise, "Drink plenty of water," "lose weight", "no eating between meals", "brush teeth after every meal "," do not eat all that do not fit in the mouth "," holy cow, that is safe for the trip a big fish and sense another common rule not even mentioned here.
It is difficult to say how much resveratrol is newly formed and how regenic food. Not can be strongly regenerated due to its derivation Tor, catabolic and antioxidant functions, the highest average life expectancy increases and leads to the absence rejuvenating cancer has increased induction or reduction of real life long. resveratrol standard diet may not be very strong because there is no appreciable regenic regulation AMPK, no real reduction in the incidence of cancer, no increase in apoptosis of cancer cells and not the extension of real life. However, many biogenesis mitochondria can be seen, but what becomes ReGenesis neogenesis is unknown because most of the researchers were aware of the difference.
Progressive companies recognize this fact and offer nutraceutical are actively seeking solutions. The basic problem is simple. When you eat more resveratrol 90% of it is sulfonated and glucuronidated in the intestine and liver via the hepatic portal system, so that the objective of water soluble renal elimination of the urinary tract. Free food unchanged resveratrol is generally less than 2 um in his one and a half-hour stage high blood plasma after ingestion. Glucuronate and sulfate derivatized resveratrol does not cross the membranes of interstitial cells and free cells on resveratrol in microsomal fractions indicate that the interstitial cells extracellular sulfatase and glucuronidase have no overall impact. This can not be true at sites of inflammation, but the whole body the desired effect does not seem to be there. Even if not, or sales numbers Intracellular free resveratrol does not appear to accumulate over time. Experiments have shown that the serum soluble free resveratrol in the range 20 um final impact of AMPK RC ch /. For example, DMSO solubilized resveratrol, when injected in mice, all causes and the desired effects downstream AMPK in brain tissue.
As mentioned above, nutraceuticals suppliers are very resourceful in their attempts to obtain serum concentrations of resveratrol in the range CR mimetic. shows a single provider, graphically, how micronization of resveratrol Resveratrol significantly increased free until much further what is necessary range AMPK activation. Other vendors are creating encapsulated, solubilized and released time formats. A supplier offers sublingual tablets delivery. The mixed with resveratrol and quercetin synergizers as Coenzyme Q, are also offered. We look forward to their data in time relative to the serum, and more Moreover, its intracellular AMPK regulation data.
Here is a quick and dirty home remedy. You can dissolve up to 500 mg of resveratrol in a 86-proof spirits, or flavored low schnaaps and more heart. The solubility depends primarily on alcohol content, so that the same should be valid for a glass of wine, but it may take a while to dissolve. Moreover, the larger the volume, the better to absorb non-intestinal tract. Take a sip, swirl around your mouth for a full minute before swallowing, relax and enjoy. The solution is what we might call the technical nanonization. It has been shown to improve absorption oral and head and neck cancer by up to 800% above methods diet, and not increasing the burden on the kidneys metabolite one iota. However, many gurus doctors who say that 10 to 20 grams of ethanol per day is good to us.
Then there is the stretch (or tension) of your imagination beyond the orbit of Pluto, the plan. Humans have circadian cycles and lunar days monthly for a reason. Anyone who has read about the circadian cycle of melatonin know what you are saying. The fact that female humans have a cycle length of the lunar cycle, receptivity, and in small groups near point all round, is no accident. The seasonal cycle has been replaced by the lunar cycle because the conditions have made possible. What happens, you ask? We never thought you asked.
The effect of the mutation is the main engine of evolution, but it is accidental, generations and usually a proposal loss, with some selective advantage. But the survival of the population support the winners in the form of multi-generational adaptation. The advantage of selecting a passage from one season to the lunar cycle must have been powerful, simply because he was forced into existence. Consider the following. Over 99% of the last two million years human evolution has been devoted slow conversion and regulate the collection, the collection of treasures, the collection of hunters, while the other fewer than 1% is called civilization. Have excellent color vision in 3-D, but the vision of the night, the night light of the full moon became a great advantage since it acquired Advanced Power wider geographical crops and easier. Being bipedal and have the ability to grip an ecosystem dryas decline were significant changes before adaptation and the possibility of death for drivers in front of proto-humans.
The dynamics of food energy created switch nutrition super full moon followed one months remaining to be trapped by the standard rate. This plays a high monthly duty cycle, and nutrition at random causing high body fat, what could easily support fertility, two weeks after the full moon, during the height of the dark new moon nights. Since no one looks ugly in the dark, and also be something else to do but stay around like blind idiots, match nutrition has been made in heaven. In addition, the social glue sticks sexual. It was already operate as part of a large creature proto-hominid brain noisy, with its ecological niche pushing a movement to brain growth even more, the representation symbolic language and a set of pre-civilization tool office waiting for a large number of people enough to tidy up things like cities, war and jacuzzis. Thus, the African scene has been created Luckily for us, all four events played before us, which shows the DNA evidence, were almost extinct.
This model is also reflected in a natural cycle of nutrients engine AMPK activity and high and low and regular cycle ReGenesis neogenesis, that could have helped us to become the primate longevity. The calving season long, the stretch of endless time of birth on sexual maturity and the creation of history, the need for seniors to pass on all that the accumulation of large brains of the next batch of stupid dimbulbs generations appear to arise generation, may have contributed to help this mixture of life extension. As part of this document, that is, if there is still no context, this kind of long speculative wannabe breath Just follow a prescribed format lunar circadian cycle.
The arrival of the high concentration of resveratrol available on the open market of bioavilable door to opportunities that actually bring the troops home. At full dose, it would bias the system toward the true CR mimetic ReGenesis AMPK mitochondria, while tenth full dose, would bias the system toward the newly formed meta-mimicry that we described in detail earlier. From neogenesis takes several days to complete, while it is much faster ReGenesis, a circadian rhythm / map of the lunar cycle forces in the system default extension ReGenesis for life could look like this: Low-dose resveratrol may be coordinated with the newly formed anti-oxidants, diet nutrient loading and / or exercise of power based in five to seven days or less, then followed by resveratrol in high doses, in conjunction with avoidance daily consumption between dinner and breakfast and / or oxygen using high-resistance exercise before breakfast in a longer period of time, about three weeks to strengthen the efficiency of mitochondria, the cleaning mobile home and a drop of glucose to fat burning. Here's something for everyone. Lounge Lizards can reap the benefits of phytonutrients model, while the minds more concerned we could improve these effects on food and exercise plans. Anyway, the organs and tissues other than cardiovascular and skeletal muscle could become the beneficiaries of resveratrol. Many changes daily, weekly and monthly theme might be considered. A plan may include one meal a day because the chronic lack ReGenesis rapid and / or exercise to help with glucose ReGenesis Nutrients of debt and / or a CR mimetic to activate AMPK loop extension life.
A study in rats very Interestingly, CR has been intermittent in the world of RC enthusiasts in your ear. The use of two-day supply ad libitum food and fasting total between rats, CR does not lead to long term, such as rats up the fasts with feasts between the days of fasting, while end with a of living comparable to the CR. This jives more or less with the downregulation of PGC-1alpha activate ReGenesis time. In fact, this study is the concrete proof of principle, by extension of life by CR can be done without it. This also jives with our idea that at least part neogenesis followed by ReGenesis, no damage to prolong life, and you can avoid poverty and lower risk of CR authentic.
An interesting question arises here. From ReGenesis is an extension of CR long-term trend the duration of the portfolio, how long is it good? By this we mean: When the mitochondria are effective, how long are effective they need before they enter into force restimulated again? In other words, how many holidays can be "to shoot" to the fast each day? " If ReGenesis is good for one week, one day a week is a small price to pay quickly. Not only that, if 18 hours of fasting, as well as 24 works, then all you have to do is pass missed breakfast once a week. End by a low dose of resveratrol that increase the effect?
We need more experience and sooner than later. But the rats alive five and older, and rats are not people (in comparison, out of time, otherwise). During metformin is contra ten years if ever, and rapamycin is too dangerous to be street legal at all times, the dimension or reality. Metformin, when used with hormone The growth for the system to switch between mechanical strength and ReGenesis neogenesis may ultimately be the greatest achievement more anti-aging rejuvenation of all time. This can really cause cells to behave more like they do in the juvenile stage. The timing, dose and evidence required in such a scenario would critical. When playing with some really big mojo, here, and would be illegal without a prescription under the care of a physician. Only people, at least in their environment early years, say, thirty years ago, could participate in this program, safely.
Fortunately, at present, resveratrol, that is freely made and know enough CR and mitochondrial neogenesis ReGenesis, to get answers instantly and human beings instead of rats. Human volunteers CR biopsies and measure through AMPK activity and mitochondrial biogenic state Krebs cycle enzymes vs. cytochrome content, allows us to control the system over time. The system is fairly well defined, now that the importance of these causality tests point instead of correlation. A wide range of experiments could be carried out quickly, and to determine what times and requirements and plans are optimal, if the sides and what other elements could be included. Ideally, we can find a schedule CR mimetic dose of resveratrol, a mimetic or a better blend of synergistic components that require no changes in lifestyle practices were wise to normal health … except for this magic pill, of course.
EPILOGUE
Not too surprisingly, there is little interference between metabolism of cancer, cardiovascular disease, diabetes, aging and nutrition / research communities for the year. Today specialization does not really allow for it, and work areas that seem distant from each other. But there are other reasons. On the one hand, the field of cancer metabolism, but the old, rather, be seen to be done, again. This has much to do with the very bitter and public battle that led to the decline of Warburg in 1956. The whole field of research has become verboten, and shirts of like "that was proven false a long time" and "not even look in this area, no more" were nearly Mantras mentality of sheep. Another reason is that, than I had thought that the connection between cancer and the extension could even exist, and even if it did, it would to the head while the fountain of youth and the murder of a monster hiding under the bed. Launched in cardiovascular and diabetes also is more than any cake icing can be sustained. But in reality, it is not too much to believe, because this is soon to become common knowledge. No one reading the three documents for review under this section can easily see that it became very obvious now for connections not to be seen by a multitude of scientists. And we do not mean small connections. We hear the big, really big.
Gregory S. Bambeck Ph.D. e-mail: gregorybambeck@yahoo.com
Michael Wolfson, JD, MBA e-mail address: mwolfson@stanfordalumni.org
Copyright © Bambeck by Michael Wolfson and Gregory June 11, 2010.
About the Author
Learn How to Play the Song “Got My Mojo Working” with http://www.vguitarlessons.cjb.net
|
|
Warrior Mojo Strung Lacrosse Head (White) #97226.WH Ultra lightweight head with reinforced Elliptical Throat for durability, additional string holes for limitless pocket versatility, a broad flat scoop design for easier ground ball pickups. Imported…. |
