Defining health and disease across biological systems organized variability

This article's primary intent is to define the earliest signs of functional pathology in biological systems while these systems still operate within generally accepted normal parameters. The goal is to enhance preventative medicine diagnostic algorithms in population and individual health. The article investigates the earliest possible sign of onset of disease in healthy biological system controlled marginal functional instability. This approach seeks to better delineate the boundaries of system homeostasis, which has long been regarded as the undisputed marker of health. The discussion presents an evolutionary perspective on health and disease, considering concepts such as homeostasis, stable non-equilibrium, marginal instability, and homeokinesis. It then advances toward the complexity of precise transitional tuning between health and disease, emphasizing the role of homeodynamic regulation. The authors propose that the cost of homeodynamic adaptation should be considered as an integral definition of metabolic expenditure, recovery time, or autonomic activation following a perturbation. Considering neurons are morphologically fractal and functionally graded, homeodynamics may provide insight into biological systems fuzzy-fractal origin of adaptation. Heart Rate Variability (HRV) is presented as an example of a hierarchical, fuzzy-fractal biological model. The optimal informational sensorium is described as an integrated measure of sufficient variability in receptor signal flow, which allows for maximized adaptive flexibility while minimizing the homeodynamic cost of marginal instability. Based on above considerations, authors proposed further research of organized structured variability as the system-level property that enables biological network to balance controlled instability while constraining energetic expenditure. The earliest detectable sign of organized variability deterioration is a reduction in scale-dependent complexity with narrowing of functional dynamic range.