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quantumhormesis

Quantum hormesis

Conventional medicine, including surgery, has come a long way in the last two millennia as humankind’s understanding of the underlying science has increased. However, although the average life expectancy has indeed risen reflecting this improved knowledge, this has only occurred in certain populations. Moreover, this has been largely attributable to better diagnosis, education, hygiene, nutrition, antibiotics, surgery and in particular, decreased childhood mortality, rather than a fundamental breakthrough in understanding what life is. Indeed defining what life is still very much debated, in particular, when looking for it beyond our own planet, and is dependent on the underlying theory of life used – the “definition-theory of life” 1. However, a consensus is emerging on the role of information in life, which has led one author to suggest that the evolution of life follows three basic stages to arrive at a definition: “self-maintainable information”, then “continuum of self-maintainable information” and finally, an individual living being can be defined as a “distinct element of the self-maintainable information’s continuum” 2. This hints that a quantum thermodynamic description is possible, but what drove the incorporation of information that led to the complex structure called life? It could be stress, which is encapsulated by a biological phenomenon called “hormesis”, whereby small amounts of stress induce a biological system to adapt to it so it is better able to deal with it, so making it more robust. As far as we can tell, stress, by invoking natural selection of particular systems, was a key component in the origins of life, as it can result in order out of chaos. A key component was and is the ability to use information: it could be argued that “what does not kill you not only makes you stronger, but longer lived and smarter” 3. If we do accept that the bioquantome is real, then it is likely that hormesis had a role in its origins, and continues to do so in relation to feedback, homeostasis and robustness.

MEDICINAL HORMESIS

A key component of the need for medicine is that we age and eventually die; if we all stayed healthy for ever, apart from accidents, we wouldn’t have much need for it. However, despite great advances in biology, and observational data suggesting that human lifespan does plateau at around 115-120 years, there is still much debate over whether or not lifespan is adaptive 4-6; it is an important question, as understanding this would provide us clues in how to live longer and impact on medicine. However, although much observational data suggests that an organism’s allotted lifespan appears to have been dictated by its evolutionary niche and is set in its genes, how long it lives can be controlled by its environment. In particular, low level stress can induce adaptability so it can better able to tolerate a variety of stressors via a process called hormesis; ageing and ultimately, death, does seem to be associated with a gradual loss of this ability 7.

To date, although medicine has also enabled many people to live longer, it has also increased the number of people developing diseases of old age, and so medicine continues to focus on treating these – but at an ever increasing cost in a kind of Faustian bargain. Rather than trying to slow down the aging process and living healthily, the emphasis is still very much on treating diseases as they occur 8. In modern societies, it seems that medicine is associated with something called “morbidity expansion”, which is where, despite a longer lifespan, a greater proportion of it is spent in ill health. However, it is also becoming clear that a modern sedentary, high calorie, low vegetable intake lifestyle seems to accelerate the ageing process, which suggests that we are using “modern” medicine to compensate. The key component that seems to be missing from our modern lifestyle is hormesis, as we have largely removed the need for physical activity, can eat as much high calorie food as we want, and tend to avoid large amounts of fruit and vegetables 9. Critically, a healthy lifestyle could greatly reduce the cost to society, and potentially, free up money for other important projects, such as space exploration 10. But the idea of living a healthy lifestyle is not new, and would imply that a healthy lifestyle could be conceived as “medicine”. For instance, in 2009, Dr Sallis suggested in a leading medical journal that exercise is medicine – an idea that has perhaps been intuitively understood for at least 2000 years 11. In 2016 it was suggested that “regular physical activity should be advocated for the prevention and first line treatment of chronic disease” 12. This is now being pushed by American College of Sports Medicine’s campaign that “Exercise is Medicine” http://www.exerciseismedicine.org.

Although hormesis seems to be something that the entire cell, indeed, organism, is involved in, one of the most important underlying mechanisms may involve “mitohormesis”, whereby mitochondrial stress initiates a beneficial response 13,14. As it is thought that mitochondria do play a key role in aging and many disease processes 15, then this would support a vast amount of data that hormesis does control longevity. This would suggest that “medicinal hormesis” is a key part of improved functional longevity, which would be expressed as “morbidity compression”, whereby people would live longer in good health, before their systems began to degrade right at the end of their lives. It may also hint at future developments on how to actually extend human lifespan.

QUANTUM BIOGENESIS

The origins of life, or abiogenesis, are still not completely clear, but it is certainly based on non-biotic chemicals that can be generated by both stellar and planetary chemistry involving ultraviolet light (UV) and so could have started in the surface of the sea, in deep sea thermal vents, or even hot springs on land – or possibly, all of them: how, however, a group of inorganic molecules became life is unclear, but it involves chemistry – powered by energy derived from either and/or a proton gradient or photon induced electron ejection 16-19. In support of this, data does suggest the UV light may have also given rise, prebiotically, to not only RNA, but also DNA building blocks 20. It has also now been suggested that UV could also be critical for life starting on exoplanets 21.

As chemistry and physics are ultimately described by quantum mechanics, as well as thermodynamics and thus entropy, it suggests that the origins of life itself must also be explainable by these disciplines, and thus, maths. For instance, life and many other “structures”, such as storms, become “ordered” because chaotic systems full of energy can form “dissipative structures”, which accelerate entropy and is an emergent property of complex systems. It has been said that life gains order by increasing disorder in the universe by converting high energy photons into low energy photons. Thus, quantum mechanics and thermodynamics could begin to explain how it started, as well as why it replicates and uses information 22-29.

Significantly it could be said that the ultimate energy currency in life is the electron – a quantum entity; the energy it carries and its exchange in biology is fundamental to all chemical reactions via “redox” (a contraction of reduction and oxidation). Modelling suggests that the ability of electrons to “tunnel” in some of the most ancient iron-sulphur electron transfer proteins is highly conserved 30. Today, quantum electron tunnelling is thought to play a pivotal role in modern mitochondria 31. Indeed, it is thought that life evolved structures, via natural selection, that quite specifically seem to exist at quantum criticality – suggesting that environment-assisted quantum transport (ENAQT) of energy, for instance, as “excitons” in photosynthesis, is universal in life 22. ENAQT seems to suggest that an external environment can, under some circumstances, enhance transport efficiency of quantum particles and obeys a universal underlying principle 32. As Albert Szent-Györgyi, the Nobel prize winner, was purported to have once said: “life is nothing but an electron looking for a place to rest”. Whether the energy initially came directly from sunlight, or from a thermal vent in the form of a proton gradient is still not precisely known, but photons, electrons and protons (which is a hydrogen nucleus without an electron), are fundamental quantum-described entities as they display wave-particle duality. This wave-particle duality has been shown for much larger entities consisting of several hundred atoms 33. It could therefore be said that as life arose in a Universe best described at the microscopic level by quantum mechanics, then the deepest description of life itself may come from this discipline.

QUANTUM AGEING

Could ageing, and thus medicine, have a bioquantome component we need to understand? It would seem to be implicit if significant quantum effects were important in how life started and evolved, in particular, via the process of mitohormesis that would enable optimal bioenergetic function in modern life.

In the classical world, ageing and death seems to be an inevitable consequence of being alive for virtually every organism on earth, and while accepted by mankind, the search for immortality is probably as old as our species. Biological immortality does have a definition, which is where the rate of mortality from senescence, or gradual loss of functionality, is uncoupled from chronological age, and some species do seem to display this, but they can still die from disease and injury and predation. In terms of evolution, it did seem that prokaryotes and some unicellular eukaryotes can in some senses be viewed as immortal, as they simply divide, producing healthy daughter cells. However, it now seems that during division, in particular under environmental stress, one daughter cell may receive already damaged components that promote cellular ageing, such as damaged proteins – termed asymmetric damage segregation – while the other starts with a healthier set of components. Thus it seems one cell, especially under stress, has better damage repair mechanisms, while the other ages because it damaged components are partitioned to it – and likely applies to modern stem cells 34. Equally, it seems, as a generalisation, simpler multicellular organisms, such as hydra or sponges, are almost immortal in the sense that they contain stem cells that can constantly produce new cells, so although individual cells die, the organism as a whole keeps going. Hence, as complexity increases, this self-regeneration ability seems to reduce, which in part seems to be an evolutionary measure to counter-act cancer 35. It is thus relevant that from a systems perspective, the aging process seems to be associated with a gradual loss of the ability to maintain this complexity as indicated by a rising frailty index and a loss of integrity, and a loss of a higher level emergent property of this system. Interestingly, in the very old, the gradual decline the resting metabolic rate (RMR) with age seems to reverse, and increases, suggesting a compensation 36. What is clear about the ageing process is that there is plenty of information of the current state of an organism to predict its future state, generally, very accurately; for the vast majority of organisms, death is deterministic. The current state of an organism will tell you a great deal about its future state.

Today, the hallmarks of ageing are recognised as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication – and lead to a gradual loss of fitness and loss of function 37. Eventually all cells die, and it seems that this process is programmed into them, such that they commit suicide when either unwanted, or become defective or just old, via a plethora of mechanisms, of which the best described is apoptosis – the dead cells are then tidily removed by other cells: there are now so many different types of cell death a committee has been set up to ensure correct nomenclature 38.

Ageing in humans is associated with pathology known as age-related diseases (ARDs), such as atherosclerosis, cancer and various dementias, and involves the sirtuins, mitochondrial function and in particular, modification of DNA expression via the process of epigenetics. Critically, the process can be slowed down by calorie restriction and many natural products, such as polyphenols, but is clearly accelerated by excess calories and a lack of exercise 39,40. Thus, the rate of ageing is modifiable, and it seems that not only is it slowed down by the right amount of stress, but also improves the organism’s fitness; these observations are defined by the concept of hormesis 7. However, perhaps the biggest question of all is whether or not ageing is programmed and adaptive, i.e., is an individual pre-programmed to have a limited lifespan, with a built in ageing clock that limits survival to ensure maximum fitness of the species, or is it simply a side product of a system that is simply not selected for by natural selection? This discussion has been going on for many years. On one side is the idea that ageing diminishes individual fitness, so could never have evolved as an adaptive program, but on the other, the existence of self-destruction programs, like apoptosis, seems to have been around for billions of years, suggesting that adaption to stress (by living longer – a concept embraced by hormesis) is important – such as during calorie restriction 41. This latter argument is embraced by the theory of “programmed senescence”; this clearly does apply to individual cells, where damaged or unwanted cells activate a suicide program, such as apoptosis. This dying for the greater good of individual cells is well known in eukaryotic multicellular organisms, but is also found prokaryotes, suggesting it evolved long before eukaryotes came into being 42,43. This has led some to suggest that programmed cell death of a more complex organism, called phenoptosis, could suggest that ageing, and thus death, are adaptive 44.

The key point here is whether or not significant quantum effects play a role in the ageing process, and thus, death. It could be argued that if the mitochondrion does have a bioquantome, as it is involved in some forms of cell death, then any degradation in its structures that enable significant quantum effects to occur would reduce its efficiency, for instance, by an increase in potentially damaging free radicals – hence triggering the process. Thus if the term “quantum mitochondrion” can be used, then it is possible that the loss of significant quantum effects do play a role in the ageing process 45. It could be argued that this could be an adaptive process to ensure biological fitness of the species.

QUANTUM INFLAMMATION

If ageing is in part determined by loss of a functional bioquantome, then it could be said that a marker for this process is inflammation. Inflammation is an old term, and literally means “setting on fire” due to association with redness and heat of damaged/infected tissues, and probably first described by Celsius in the first century AD, while Galen added loss of function a bit later, but it was Hunt in the 1700s who realised it was both a reaction to damage and a defence against injury 46. Thus inflammation is perhaps, serendipitously, based on the concept of heat, which is of course fundamental to thermodynamics. A characteristic of ageing in many complex organisms, like humans, is rising inflammatory tone. Inflammation is a well described homeostatic mechanism initiated by damage resulting in oxidative stress. It is in fact so linked to ageing that the term “inflamm-aging” has been coined, and it is associated with changes in mitochondrial function 47,48.

A potential explanation of inflammation’s association with age-related disease is that it is the price that organisms pay for stress-related redox signalling involving the mitochondrion, which is biased towards youth and reproduction, but in older age, becomes increasingly damaging; during inflammation, mitochondria are reprogrammed to help defend against infection – which is helpful when young, but becomes damaging with age 49. One of the effects of calorie restriction is to suppress inflammation – a process involving the sirtuins, which are a group of ancient proteins that seem to play a key role in balancing longevity with stress and energy availability 50. At the simplest level, the process of inflammation and immunity involves the redirection of electrons towards defence and repair, but in the process, can induce damage to the host organism – but this might be necessary. Thus the rate of ageing is thus modified by the flow of electrons in response to environmental conditions. As excessive electrons, in the form of too much food, accelerate ageing, while limiting them, as in calorie restriction, slows ageing; it is likely this represents a fundamental principle that first arose when life began.

This may suggest a much deeper understanding of the origins of life, and its evolution in quantum terms that underlie thermodynamics, could shed light on what inflammation actually represents. As mitochondria may well rely on quantum processes, in particular, to channel electrons, and are key in the inflammatory process, then it could be that a gradual degradation in this process might underlie the aging process 51. Given that natural selection is key, it could be argued that inflammation actually represents an echo of the origins of life whereby disruption of electron flow sends a signal to either repair and rebuild, or destroy a system that has become hard-wired through genetics – as a disruptive system could damage other systems. In effect, inflammation controls an adaptive ageing process, which is based on efficient quantum principles, such as tunnelling. If a system cannot adapt, it is removed. The implication is that this quantum efficiency would apply at a global level to sustain life as an entropic accelerator, meaning that individual species, if they fail the stress adaptation test, are removed in favour of more adaptable ones (Nunn et al., Quantum inflammation and the control of life and death, soon to be submitted).

Quantum ageing could therefore be defined as an adaptive process triggered by the gradual loss of the ability to maintain quantum processes, probably related to loss of protein structure and increasing electron leakage resulting in rising oxidative stress, which results in the natural selection of fitter organisms or species. In turn, quantum inflammation is the process whereby damaged-induced loss of structure, which results in the redirection of electrons, initiates a repair or die strategy and is thus closely linked to ageing (Nunn et al, Quantum inflammation and the control of life and death, soon to be submitted). One theory that could support it is the thermodynamic dissipation theory on the origins of life, where it is thought UV light may have played a key role in the selective process of the earliest self-replicating molecules that stored information by dissipating solar energy into heat; molecules that could act as sunscreens, and dissipate energy safely, might have been selected for 28,52. As Radoslaw Piast has suggested about how life might be defined relating to its evolution and the ability of a simple system to maintain homeostasis via feedback mechanisms to ensure self-maintenance 2, it might also hint that a mechanism for the removal of defective systems may have also evolved to protect the ones that were functional. This might hint that ageing is indeed adaptive, and that in may not just be modifiable in the short term, but could indeed be controlled to extend lifespan beyond what is currently programmed into most organisms.

BIOQUANTOME MODULATORS

As medicine refers both to the practice, and to compounds used in its practice, then it is possible that the practice of medicine is already manipulating the bioquantome to bring about optimal health. For example exercise may provide the requisite stress to enhance natural selection of the most efficient systems, for instance, in bioenergetics that may rely on supraquantum processes. Equally, many drugs could also, under some circumstances, either directly modulate, or induce, alterations that bring about improvements in the bioquantome. The existence of coherent excitation in living cells has long been suggested, in particular, by Herbert Fröhlich, which involves resonance between mitochondrial and the microtubule skeleton of the cell and has been called Fröhlich coherence 53. At the deepest level as chemistry is ultimately describable by quantum mechanics, then it follows that biochemistry might also be defined in the same way, which may suggest that on some level, so are the actions of drugs.

Conventional pharmacology is generally discussed in classical terms, for instance, a drug, because of its specific shape and chemical composition, is thought to bind to and modulate a particular receptor, channel, or enzyme that is over or under-active in a particular disease condition, so helping to restore homeostasis. For example, drugs called ACE inhibitors, inhibit an enzyme that if over-active, increases blood pressure. It is therefore interesting that drug companies are increasingly turning to computer aided drug design (CADD) based on quantum mechanics, rather than the older practice of molecular mechanics, which is based on a more classical ball and spring model and does not model electrons 54. As it has been suggested that quantum mechanical principles may well underlie how a compound interacts with its target, for instance, an odour molecule with an odour receptor via its quantum defined molecular vibrational properties, rather than purely its shape 55,56, then it could be inferred that some drugs are actually using fundamental quantum principles in order to bring about their benefit. But this does raise the possibility that this very direct targeting, although it is describable through the quantum principles underlying chemistry, it may not be manipulating the bioquantome in a way that is always going to be beneficial. It could well be that one may need to look at the supraquantum level, which biology may have enhanced for its own benefit. Notably, many effective drugs were originally based on natural products, but today it is becoming increasingly difficult to find and develop new drugs, as many promising candidates turn out to have many side effects and are withdrawn – making it a very expensive process. It is also noteworthy that many compounds are being “repurposed” to treat different diseases. What is potentially informative is that many natural and man-made products seem to have a broad range of medicinal properties and modulate multiple targets. For example salicylic acid, the main component of aspirin; although it was originally thought to work mainly through one enzyme involved in inflammation, it actually modulates many targets, including mitochondria – making its mode of action much less obvious. It is even used in proprietary sunscreens, and is key in the plant stress response. Given its ability to act as a sunscreen, it could act by being able to dissipate excessive energy via quantum resonance – which might explain how many natural products work as they are also natural sunscreens due to their molecular structures containing double bonds (Nunn et al, submitted). An important principle here is that certainly in the photosynthetic process, the ability to dissipate excess energy using fundamental quantum principles via a form of quantum resonance may well be important 57. Another mechanism is that many compounds are hormetic, which has been suggested for some time to be a potential way in which they work 58. A key point here is that the concentration of the drug is important, as it can have different effects at different concentrations, for instance, low levels may be directly protective, but higher levels may mildly activate a stress response, while still higher levels may cause too much disruption and certainly in plants, become anti-pathogenic or even anti-cancer.

In summary, although the interaction of many potentially medicinal compounds with their ascribed cellular targets could be describable at the fundamental quantum mechanical level, if the bioquantome is real, and life has utilised supraquantum effects, then some classes of drugs that could potentially manipulate this – such as some compounds that act as sunscreens, then their effects may in part be due to modulation of the bioquantome.

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quantumhormesis.txt · Last modified: 2019/09/26 23:09 by missionfmb