The intelligence paradox; will ET get the metabolic syndrome? Lessons from and for Earth

Mankind is facing an unprecedented health challenge in the current pandemic of obesity and diabetes. We propose that this is the inevitable (and predictable) consequence of the evolution of intelligence, which itself could be an expression of life being an information system driven by entropy. Because of its ability to make life more adaptable and robust, intelligence evolved as an efficient adaptive response to the stresses arising from an ever-changing environment. These adaptive responses are encapsulated by the epiphenomena of "hormesis", a phenomenon we believe to be central to the evolution of intelligence and essential for the maintenance of optimal physiological function and health. Thus, as intelligence evolved, it would eventually reach a cognitive level with the ability to control its environment through technology and have the ability remove all stressors. In effect, it would act to remove the very hormetic factors that had driven its evolution. Mankind may have reached this point, creating an environmental utopia that has reduced the very stimuli necessary for optimal health and the evolution of intelligence - "the intelligence paradox". One of the hallmarks of this paradox is of course the rising incidence in obesity, diabetes and the metabolic syndrome. This leads to the conclusion that wherever life evolves, here on earth or in another part of the galaxy, the "intelligence paradox" would be the inevitable side-effect of the evolution of intelligence. ET may not need to just "phone home" but may also need to "phone the local gym". This suggests another possible reason to explain Fermi's paradox; Enrico Fermi, the famous physicist, suggested in the 1950s that if extra-terrestrial intelligence was so prevalent, which was a common belief at the time, then where was it? Our suggestion is that if advanced life has got going elsewhere in our galaxy, it can't afford to explore the galaxy because it has to pay its healthcare costs

Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

The metabolic syndrome may have its origins in thriftiness, insulin resistance and one of the most ancient of all signalling systems, redox. Thriftiness results from an evolutionarily-driven propensity to minimise energy expenditure. This has to be balanced with the need to resist the oxidative stress from cellular signalling and pathogen resistance, giving rise to something we call 'redox-thriftiness'. This is based on the notion that mitochondria may be able to both amplify membrane-derived redox growth signals as well as negatively regulate them, resulting in an increased ATP/ROS ratio. We suggest that 'redox-thriftiness' leads to insulin resistance, which has the effect of both protecting the individual cell from excessive growth/inflammatory stress, while ensuring energy is channelled to the brain, the immune system, and for storage. We also suggest that fine tuning of redox-thriftiness is achieved by hormetic (mild stress) signals that stimulate mitochondrial biogenesis and resistance to oxidative stress, which improves metabolic flexibility. However, in a non-hormetic environment with excessive calories, the protective nature of this system may lead to escalating insulin resistance and rising oxidative stress due to metabolic inflexibility and mitochondrial overload. Thus, the mitochondrially-associated resistance to oxidative stress (and metabolic flexibility) may determine insulin resistance. Genetically and environmentally determined mitochondrial function may define a 'tipping point' where protective insulin resistance tips over to inflammatory insulin resistance. Many hormetic factors may induce mild mitochondrial stress and biogenesis, including exercise, fasting, temperature extremes, unsaturated fats, polyphenols, alcohol, and even metformin and statins. Without hormesis, a proposed redox-thriftiness tipping point might lead to a feed forward insulin resistance cycle in the presence of excess calories. We therefore suggest that as oxidative stress determines functional longevity, a rather more descriptive term for the metabolic syndrome is the 'lifestyle-induced metabolic inflexibility and accelerated ageing syndrome'. Ultimately, thriftiness is good for us as long as we have hormetic stimuli; unfortunately, mankind is attempting to remove all hormetic (stressful) stimuli from his environment

The Hormesis of Thinking: A Deeper Quantum Thermodynamic Perspective?

We are able to read this because of quantum and thermodynamic principles that via an inorganic proton gradient, possibly generated 4.2 billion years ago, gave rise to a system that has an awareness of time and space by using energy to integrate information. Life can be described as a dissipative system driven by an energy gradient that uses information to positively reinforce its self-sustaining structure, which in turn increases its non-linear decisional capacity. Key in the evolution of life has been stress coupled to natural selection, which usually meant an increased demand for energy. As hormesis describes the adaptive response to stress, we propose that hormesis embraces not only the evolution of life, but that of intelligence itself, as natural selection would favour systems that enhances its efficiency. A component of the hormetic response in eukaryotes is the mitochondrion, which itself relies on quantum effects such as tunnelling. This suggests that quantum effects control the stability of individual cells as well as long-lived cellular networks. Hormesis, which can be anti-inflammatory, is therefore key in maintaining the functional stability of complex systems, including the brain. In contrast, a lack of classical hormetic factors, such as physical activity, plant polyphenols, or calorie restriction, will lead to accelerated cognitive decline, which is associated with increased inflammation. However, there may be another previously unidentified factor that could also be considered hormetic, and that is thinking itself. Here we propose that the process of “thinking”, and managing complex movement, induces “stress” in the neuronal system and is therefore in itself part of maintaining cognitive health and reserve throughout life. In effect, the right amount of thinking and information processing can beneficially induce adaptation, and this itself could be explainable by quantum thermodynamics

Endocannabinoids in neuroendopsychology: multiphasic control of mitochondrial function

The endocannabinoid system (ECS) is a construct based on the discovery of receptors that are modulated by the plant compound tetrahydrocannabinol and the subsequent identification of a family of nascent ligands, the 'endocannabinoids'. The function of the ECS is thus defined by modulation of these receptors-in particular, by two of the best-described ligands (2-arachidonyl glycerol and anandamide), and by their metabolic pathways. Endocannabinoids are released by cell stress, and promote both cell survival and death according to concentration. The ECS appears to shift the immune system towards a type 2 response, while maintaining a positive energy balance and reducing anxiety. It may therefore be important in resolution of injury and inflammation. Data suggest that the ECS could potentially modulate mitochondrial function by several different pathways; this may help explain its actions in the central nervous system. Dose-related control of mitochondrial function could therefore provide an insight into its role in health and disease, and why it might have its own pathology, and possibly, new therapeutic directions

Informing the Cannabis Conjecture: From Life’s Beginnings to Mitochondria, Membranes and the Electrome - A Review

Before the late 1980s, ideas around how the lipophilic phytocannabinoids might be working involved membranes and bioenergetics as these disciplines were “in vogue”. However, as interest in genetics and pharmacology grew, interest in mitochondria (and membranes) waned. The discovery of the cognate receptor for tetrahydrocannabinol (THC) led to the classification of the endocannabinoid system (ECS) and the conjecture that phytocannabinoids might be “working” through this system. However, the how and the “why” they might be beneficial, especially for compounds like CBD, remains unclear. Given the centrality of membranes and mitochondria in complex organisms, and their evolutionary heritage from the beginnings of life, revisiting phytocannabinoid action in this light could be enlightening. For example, life can be described as a self-organising and replicating far from equilibrium dissipating system, which is defined by the movement of charge across a membrane. Hence the building evidence, at least in animals, that THC and CBD modulate mitochondrial function could be highly informative. In this paper, we offer a unique perspective to the question, why and how do compounds like CBD potentially work as medicines in so many different conditions? The answer, we suggest, is that they can modulate membrane fluidity in a number of ways and thus dissipation and engender homeostasis, particularly under stress. To understand this, we need to embrace origins of life theories, the role of mitochondria in plants and explanations of disease and ageing from an adaptive thermodynamic perspective, as well as quantum mechanics

Thermodynamics and Inflammation: Insights into Quantum Biology and Ageing

Inflammation as a biological concept has been around a long time and derives from the Latin “to set on fire” and refers to the redness and heat, and usually swelling, which accompanies injury and infection. Chronic inflammation is also associated with ageing and is described by the term “inflammaging”. Likewise, the biological concept of hormesis, in the guise of what “does not kill you, makes you stronger”, has long been recognized, but in contrast, seems to have anti-inflammatory and age-slowing characteristics. As both phenomena act to restore homeostasis, they may share some common underlying principles. Thermodynamics describes the relationship between heat and energy, but is also intimately related to quantum mechanics. Life can be viewed as a series of self-renewing dissipative structures existing far from equilibrium as vortexes of “negentropy” that ages and dies; but, through reproduction and speciation, new robust structures are created, enabling life to adapt and continue in response to ever changing environments. In short, life can be viewed as a natural consequence of thermodynamics to dissipate energy to restore equilibrium; each component of this system is replaceable. However, at the molecular level, there is perhaps a deeper question: is life dependent on, or has it enhanced, quantum effects in space and time beyond those normally expected at the atomistic scale and temperatures that life operates at? There is some evidence it has. Certainly, the dissipative adaptive mechanism described by thermodynamics is now being extended into the quantum realm. Fascinating though this topic is, does exploring the relationship between quantum mechanics, thermodynamics, and biology give us a greater insight into ageing and, thus, medicine? It could be said that hormesis and inflammation are expressions of thermodynamic and quantum principles that control ageing via natural selection that could operate at all scales of life. Inflammation could be viewed as a mechanism to remove inefficient systems in response to stress to enable rebuilding of more functional dissipative structures, and hormesis as the process describing the ability to adapt; underlying this is the manipulation of fundamental quantum principles. Defining what “quantum biological normality” is has been a long-term problem, but perhaps we do not need to, as it is simply an expression of one end of the normal quantum mechanical spectrum, implying that biology could inform us as to how we can define the quantum world

Inflammatory modulation of exercise salience: using hormesis to return to a healthy lifestyle

Most of the human population in the western world has access to unlimited calories and leads an increasingly sedentary lifestyle. The propensity to undertake voluntary exercise or indulge in spontaneous physical exercise, which might be termed "exercise salience", is drawing increased scientific attention. Despite its genetic aspects, this complex behaviour is clearly modulated by the environment and influenced by physiological states. Inflammation is often overlooked as one of these conditions even though it is known to induce a state of reduced mobility. Chronic subclinical inflammation is associated with the metabolic syndrome; a largely lifestyle-induced disease which can lead to decreased exercise salience. The result is a vicious cycle that increases oxidative stress and reduces metabolic flexibility and perpetuates the disease state. In contrast, hormetic stimuli can induce an anti-inflammatory phenotype, thereby enhancing exercise salience, leading to greater biological fitness and improved functional longevity. One general consequence of hormesis is upregulation of mitochondrial function and resistance to oxidative stress. Examples of hormetic factors include calorie restriction, extreme environmental temperatures, physical activity and polyphenols. The hormetic modulation of inflammation, and thus, exercise salience, may help to explain the highly heterogeneous expression of voluntary exercise behaviour and therefore body composition phenotypes of humans living in similar obesogenic environments

SARS-CoV-2 and EBV; the cost of a second mitochondrial "whammy"?

We, and others, have suggested that as the SARS-CoV-2 virus may modulate mitochondrial function, good mitochondrial reserve and health could be key in determining disease severity when exposed to this virus, as the immune system itself is dependent on this organelle's function. With the recent publication of a paper showing that long COVID could be associated with the reactivation of the Epstein Barr Virus, which is well known to manipulate mitochondria, we suggest that this could represent a second mitochondrial "whammy" that might support the mitochondrial hypothesis underlying COVID-19 severity and potentially, the occurrence of longer-term symptoms. As mitochondrial function declines with age, this could be an important factor in why older populations are more susceptible. Key factors which ensure optimal mitochondrial health are generally those that ensure healthy ageing, such as a good lifestyle with plenty of physical activity. The ability of viruses to manipulate mitochondrial function is well described, and it is now also thought that for evolutionary reasons, they also manipulate the ageing process. Given that slowing the ageing process could well be linked to better economic outcomes, the link between mitochondrial health, economics, COVID-19 and other viruses, as well as lifestyle, needs to be considered

Understanding Long COVID; Mitochondrial Health and Adaptation—Old Pathways, New Problems

Many people infected with the SARS-CoV-2 suffer long-term symptoms, such as “brain fog”, fatigue and clotting problems. Explanations for “long COVID” include immune imbalance, incomplete viral clearance and potentially, mitochondrial dysfunction. As conditions with suboptimal mitochondrial function are associated with initial severity of the disease, their prior health could be key in resistance to long COVID and recovery. The SARs virus redirects host metabolism towards replication; in response, the host can metabolically react to control the virus. Resolution is normally achieved after viral clearance as the initial stress activates a hormetic negative feedback mechanism. It is therefore possible that, in some individuals with prior sub-optimal mitochondrial function, the virus can “tip” the host into a chronic inflammatory cycle. This might explain the main symptoms, including platelet dysfunction. Long COVID could thus be described as a virally induced chronic and self-perpetuating metabolically imbalanced non-resolving state characterised by mitochondrial dysfunction, where reactive oxygen species continually drive inflammation and a shift towards glycolysis. This would suggest that a sufferer’s metabolism needs to be “tipped” back using a stimulus, such as physical activity, calorie restriction, or chemical compounds that mimic these by enhancing mitochondrial function, perhaps in combination with inhibitors that quell the inflammatory response

Cell-Cell Death Communication by Signals Passing Through Non-Aqueous Environments: A Reply

The effects of the emission of low intensity light from cells and organelles, known as biophotons, or ultraweak photon emission, are not well understood and subject to debate. Potapovich & Kostyuk recently proposed that the induction of oxidative stress generates non-chemical death signals which can induce cell death in neighbouring, chemically isolated cells (termed detector cells). Given the significance of these results, here we attempt to replicate their findings. We found treatment of “inductor cells” with duroquinone dissolved in ethanol does indeed induce significant cell death in neighbouring “detector” cells relative to distant control cells (64.53% ± 14.42 vs 99.72% ± 6.09 cell viability), closely reproducing their original results. However, this was no longer true if the induction drug was dissolved in a less volatile solvent, suggesting that their original findings may have been a result of volatile solvent-based transmission as opposed to light-based non-chemical signalling