UCLA

Despite widespread and striking examples of physiological oscillations, their functional role is often unclear. Even glycolysis, the paradigm example of oscillatory biochemistry, has seen questions about its oscillatory function. Here, we take a systems approach to argue that oscillations play critical physiological roles, such as enabling systems to avoid desensitization, to avoid chronically high and therefore toxic levels of chemicals, and to become more resistant to noise. Oscillation also enables complex physiological systems to reconcile incompatible conditions such as oxidation and reduction, by cycling between them, and to synchronize the oscillations of many small units into one large effect. In pancreatic β-cells, glycolytic oscillations synchronize with calcium and mitochondrial oscillations to drive pulsatile insulin release, critical for liver regulation of glucose. In addition, oscillation can keep biological time, essential for embryonic development in promoting cell diversity and pattern formation. The functional importance of oscillatory processes requires a re-thinking of the traditional doctrine of homeostasis, holding that physiological quantities are maintained at constant equilibrium values, a view that has largely failed in the clinic. A more dynamic approach will initiate a paradigm shift in our view of health and disease. A deeper look into the mechanisms that create, sustain and abolish oscillatory processes requires the language of nonlinear dynamics, well beyond the linearization techniques of equilibrium control theory. Nonlinear dynamics enables us to identify oscillatory ('pacemaking') mechanisms at the cellular, tissue and system levels.