Natural Powerful Antioxidants

Demise of the Self Correcting Machine

After the previous chapter, you might be forgiven for supposing that the mitochondrial theory of ageing is claptrap. After all, most of its predictions seem utterly false. One prediction is that antioxidants should prolong maximal lifespan, and this does not seem to be true. Another is that mitochondrial DNA mutations should accumulate with ageing, but only the least important ones actually do. Another is that the proportion of free radicals escaping the respiratory chains is constant, so lifespan should vary with metabolic rate but this is only true in general, and fails to explain exceptions like bats, birds, humans, and the exercise paradox (the fact that athletes, who consume more oxygen over a lifetime, don't age faster than couch potatoes). In fact, the only prediction of the original theory that seems to be true is that mitochondria are the main source of free radicals in the cell. Hardly the lineaments of a vigorous, healthy theory. It's time to return to an idea that we...

Mitochondrial mutations

Harman argued that, because free radicals are so reactive, those escaping from the respiratory chains should mainly affect the mitochondria themselves they should react on the spot, where they were produced, and not damage distant locations very much. He then asked, quite perceptively, whether the gradual decay of mitochondria with increasing age 'might be mediated in part through alteration of mitochondrial DNA functions ' The chain of effect would be as follows free radicals escape the respiratory chains and attack the adjacent mitochondrial DNA, causing mutations that undermine mitochondrial function. As mitochondria decay, the performance of the cell as a whole declines, leading to the traits of ageing. So what are the chances that mutations would affect the respiratory chain proteins It's overwhelmingly likely. We have seen that thirteen of the core respiratory proteins are encoded by mitochondrial DNA, which is anchored to the membrane right next to the respiratory chains. Any...

Why mitochondria need genes

The mitochondrion is inefficient and in danger of damaging itself. To rectify the situation, it needs to make more cytochrome oxidase, so it sends a message to the genes Make more cytochrome oxidase How would this message operate The signal might well be the free radicals themselves a sudden burst of free radicals can alter gene activity through the action of transcription factors that leap into action only when oxidized by free radicals (they are said to be 'redox-sensitive'). In other words, if there is not enough cytochrome oxidase, electrons back up in the chain and leak out as free radicals. The sudden appearance of free radicals is interpreted by the cell as a signal that there is not enough cytochrome oxidase. It responds accordingly by making some more.1 Let's imagine that the genes are in the nucleus. The message arrives, and the nucleus sends orders to make more copies of cytochrome oxidase. It directs the newly minted proteins to the...

Down the maternal line

The first critical difference between mitochondrial and nuclear DNA is the mutation rate. On average, the mutation rate of mitochondrial DNA is nearly twenty times faster than nuclear DNA, although the actual rate varies according to the genes sampled. This fast mutation rate equates to a fast rate of evolution (but we should beware of always equating the two, as we'll see later). The fast rate of evolution stems from the proximity of mitochondrial DNA to the free radicals generated in cellular respiration. The effect is to magnify the differences between races. While nuclear DNA can barely distinguish between chimps and humans, the mitochondrial clock ticks fast enough to reveal differences accumulating over tens of thousands of years, just the right speed for peering into human prehistory.

The retrograde response

We have seen that the mitochondria operate a sensitive feedback system, in which the leaking free radicals themselves act as signals to calibrate and adjust performance. But the fact that free radicals play an integral part in mitochondrial function does not mean that they are not toxic too. Clearly they are, even if rather less so than is shouted about in health magazines. Lifespan does correlate with the rate of free-radical leakage from respiratory chains. While a good correlation doesn't necessarily imply a causal link, it's hard to claim causality in the absence of any correlation at all. If two factors are not linked in any way, then one can hardly be said to 'cause' the other and there are remarkably few, if any, other factors which correlate with lifespan across radically different groups, such as yeast, nematodes, insects, reptiles, birds, and mammals. For the sake of argument, let's assume that free radicals do cause ageing. How can we square their signalling role with a...

Cell Possible Cure For Old

Ageing and age-related diseases can be ascribed to mitochondrial free-radical leakage. Unfortunately, or perhaps fortunately, the way in which the body deals with free-radical leakage from the mitochondria is far more complex than the rather naive early formulation of the mitochondrial theory would have us believe. Rather than simply causing damage and destruction, free radicals play a vital role in keeping respiration fine-tuned to needs, and in signalling respiratory deficiencies to the nucleus. This is possible because the proportion of free radicals leaking from the mitochondria fluctuates. High levels of free radicals signal respiratory deficiency, which can be corrected by compensatory changes in the activity of mitochondrial genes. If the deficiency is irreversible, and the mitochondrial genes are unable to re-establish control over respiration, then the overload of free radicals oxidizes the membrane lipids, which collapses the membrane potential. Mitochondria that lose their...

Biological Impact of Radiation

Indirect effect results from an x-ray photon cleaving the water molecule. Radiolysis of water can produce not only ions but also free radicals. The latter are extremely reactive, can act as a strong oxidizing agent, and have the ability to move through the cell membrane to reach the DNA molecule. In the presence of oxygen, this process is enhanced. Since approximately 80 of a living human is composed of water, free radicals are the primary cause of biological damage.

The Mitochondrial Theory of Ageing

Denham Harman, pioneer of free radicals in biology, first proposed the mitochondrial theory of ageing in 1972. Harman's central point was simple the mitochondria are the main source of oxygen free radicals in the body. Such free radicals are destructive, and attack the various components of the cell, including the DNA, proteins, lipid membranes, and carbohydrates. Much of this damage could be repaired or replaced in the usual way by the turnover of cell components, but hotspots of damage, most notably the mitochondria themselves, would be harder to protect simply by consuming dietary antioxidants. Thus, spake Harman, the rate of ageing and the onset of degenerative diseases should be determined by the rate of free-radical leakage from mitochondria, combined with the cell's innate ability to protect against, or repair, the damage. Harman based his argument on the correlation between metabolic rate and lifespan in mammals. He explicitly labelled the mitochondria the 'biological clock'....

Quantum Treatment

In addition to therapy, quantum prophylaxis can also be performed based on the techniques of quantum therapy. For instance, prophylaxis of disease relapses in periodical exacerbation requires quantum treatment at early stage of an epidemic. There are also some interesting reports on application of quantum dot in vaccinology. Upadhyay investigated how mild local hyperthermia could be used for transdermal-immunization 53 . Upadhyay said that hyperthermia enhanced transdermal-immunization procedure was likely to have higher compliance as it did not cause any pain or visible damage to the skin 53 . Quantum rehabilitation also makes use of quantum therapy techniques. The use of quantum medicine technologies can assist fasten patient rehabilitation period after complex operations, radiation nor chemical exposures. The most broadly use quantum rehabilitation is for cardiological problem 54-55 . The quantum gravitational therapy is the broadly mentioned method. This technique is a complex...

Oxygen

Nick Lane studied biochemistry at Imperial College, University of London. His doctoral research, at the Royal Free Hospital, was on oxygen free-radicals and metabolic function in organ transplants. Dr Lane is an honorary senior research fellow at University College London and formerly strategic director at Adelphi Medi Cine, a medical multimedia company based in London, where he was responsible for developing interactive approaches to medical education. Articles by Nick Lane have been published in numerous international journals, including Scientific American, New Scientist, The Lancet and the British Medical Journal. He lives in London.

Oxford

4A searching analysis of the role played by free radicals in senescence crammed with interesting information, supported by an eclectic choice of references to the recent literature a worthy effort with a clearly argued message, full of informative and entertaining details.' 'Lane's book is an extraordinary orchestration of disparate scientific disciplines, connecting the origins of life on earth with disease, age and death in human beings. In his finale, he tells us many things we ought to know about antioxidants and diet

Genes and networks

If, owing to some developmental abnormality,62 the patterning of the axial skeleton is upset so, too, there is a tendency to develop childhood cancers. These are examples of uncontrolled cell proliferations, which in this case originate in the developing embryo. For mammals, departure from seven spells lethality. Moreover, in mammals some cancers may owe their initiation to the production of highly reactive molecules (known as free radicals). In the mammals, at least, the free radicals are an unavoidable by-product of an active metabolism. It may be no coincidence that the few exceptions to the rule of seven in neck vertebrae are in the metabolically sluggish animals, such as the torpid sloth. In this sense the rule of seven in mammalian necks is a good example of stabilizing selection, and may be the 'price' to pay in ensuring the effective development of very complex organisms. Such a constraint has, therefore, its costs, but when we see the diversity of mammals it seems that a...

Freeradical signal

We discussed the leakage of free radicals from the chain in Part 3. Paradoxically, the rate of free-radical leakage does not correspond to the rate of respiration, as one might think intuitively, but rather depends on the availability of electrons (ultimately derived from food) and oxygen. Because these factors vary continuously, free-radical production shifts according to circumstances. Sudden bursts of free-radical production can affect the behaviour of the cell. fuel (and plenty to meet this demand), there is a fast flux of electrons down the respiratory chain to oxygen. In these circumstances, relatively few free radicals leak from the chain. This is because they are more likely to pass down the line of least resistance, from one electron acceptor to the next in the chain, and finally to oxygen. Blackstone describes the chain in these circumstances as a well-insulated wire, through which electricity flows as a current of electrons. So, fast...

Proton leak

Once our prototype mammal has digested his food, caught so easily with his newfound aerobic prowess, he goes to sleep. Beyond replenishing his reserves of glycogen and fat, there is little call to expend energy. His mitochondria fill up with electrons extracted from food. This is a dangerous situation. The respiratory chains in the mitochondria become packed with electrons, because there is only a sluggish electron flow. At the same time, there is plenty of oxygen around, as the blood flow can't be diverted. In these conditions, electrons easily escape from the respiratory chains to form reactive free radicals, which can damage the cell. What might be done According to Martin Brand in Cambridge, one answer might be to waste energy by keeping the whole system ticking over. The danger from free radicals is at its greatest when there is no electron flow down the chain. Electrons pass most readily on to the next complex in the chain, and so tend to react with oxygen only when that complex...