What is Volume 1 About?

The first volume of this book explores areas of modern physics with major implications for biology and medicine. Areas surveyed include thermodynamics applied to bioenergetics, quantum biology, complexity and chaos theories. Particularly useful is the notion of phase transitions sinceit reduces the number of variables in a complex system to the essential few. This has led to the introduction of order and control parameters with bifurcation points where instabilities built into such systems cause catastrophic changes in their behavior. In the context of human physiology, a bifurcation point is tantamount to the transition from health to disease. This powerful methodology has found applications beyond physics, e.g.in materials engineering, sociology, and even environmental science.  A central theme connecting all chapters in Volume 1 is the importance of modern physics in gaining quantitative insights into biological systems. Modern physics offers an integrated representation of the hierarchical, interconnected, and synchronized organization of living matter.

A quantitative framework to describe the body’s responses to external stresses is proposed as a multi-dimensional fitness function analogous to the thermodynamic free energy.  In volume 2, we refer to it as the Physiological Fitness Landscape (PFL) and tie this to the -omics generated Big Data analyzed by AI algorithms. Advances physics has made in understanding complex natural phenomena include areas such as quantum biology, which explained effects of electromagnetic fields on living systems (e.g. photosynthesis) and large-scale phenomena such as organism-wide synchronization through biological coherence. Of particular importance is the theory of quantum metabolism, which employs empirical quantization rules for mitochondrial enzymes analogously to the Debye theory of vibrations in solids. With mathematical elegance, quantum metabolism elucidated the origin of allometric scaling laws of physiology (relating metabolic ratesto body weight), a problem unresolved for over a century. Equally significant is the conclusion that inefficient energy production, characteristic of disease states (e.g.cancer) manifests isometric scaling laws (i.e. linear dependence of metabolic rate on body weight) while optimum states of health result from quantum metabolism’s synchronized energy production.

It is this author’s strongly held conviction that these multidisciplinary approaches support problem solving in clinical medicine, especially when integrated with Big Data and AI algorithms. This is the bridge to the bright future of medicine, which will be personalized, predictive, and precision-based.

What is Volume 2 About?

Volume 2 focuses on the metabolic basis for the development of chronic diseases of aging including diabetes, cardiovascular disease, dementias, and cancers through complex interactions of multiple parameters. We explore the intersections of the body’s stress response, the biology of time as mediated by molecular clocks and nuclear hormone receptors, changes in intestinal microbiota composition and diversity, insulin signaling and resistance, and mitochondrial function and malfunction. The interactions of these aspects are proposed as a model of the evolution of the chronic diseases of aging and promotion of health, termed the Physiological Fitness Landscape (PFL).

Circadian biology is defined as an elegantly orchestrated synchronization of metabolism, within and across tissues and organ systems. The PFL speaks to this exquisitely beautiful organization of metabolic features, which in an optimal state, reflects a synchronized precision of the human body. Chronic diseases cause spatial and temporal desynchronization of organ systems that interfere with energy production. As such there are three fundamental metabolic characteristics of the PFL that define “fitness”: redox, free energy, and acid-base balance. In the state of health, each is maintained within a narrow physiological range.

Volume 2 speaks to the transition from health to a disease state, which involves prolonged and/or exaggerated stress. Stress, a function of age and personal history may originate in the mind or body and shift metabolism out of balance. Stress drives an immune response that intersects with the immune system, gut microbiome, and insulin signaling and can be vastly exacerbated by redox-mediated inflammation. Uncontrolled redox causes local inflammation to spread throughout the body, lowers the thresholds for future stress responses and primes the body for exaggerated, chronic activation of the autonomic nervous system, kicking the hormonal branches of the neuroendocrine stress response into overdrive. Chronically, a prolonged stress response disrupts the natural circadian cycles of insulin secretion and signaling, which can cause pathological insulin resistance to ensue. Since insulin signaling is an important circadian regulator of clock-controlled rhythms, persistent hyperinsulinemia, a consequence of disrupted patterns of insulin secretion, promotes the loss of synchronized metabolism within and between tissues of the body. The stress response, deranged microbiota, disrupted redox, inflammation, insulin resistance and perturbation of molecular clocks/circadian biology all amplify one another in a vicious cycle, and physiological fitness therefore declines in a manner tantamount to the aging process.

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Metabolisim & Medicine