Inter-modulating Multi-frequency Rhythms

Abstract

Circadian rhythms are characterized by their amplitude, phase, and period when they differ from 24 hours, in addition to the rhythm-adjusted mean (MESOR). Non-sinusoidal periodic signals can be described by the amplitude and phase of additional harmonic terms. Alterations in these characteristics are a hallmark of ageing and disease. Time-specified reference values in health make it possible to diagnose impending disease and to initiate treatment early, as illustrated for blood pressure and endpoints of heart rate variability. Often, there is a bidirectional relationship between disease risk and circadian disruption at the molecular as well as at the organismic level. Disease risk assessment and chronotherapy also benefit from the additional consideration of ultradian rhythms, used for pacing and pulsatile drug delivery, and infradian rhythms. The derivation of circadian reference values in health, combined with an assessment of the broad multi-frequency time structure, helps in the early diagnosis of disease and the optimization of treatment through timing. Understanding the role played by clock genes in cellular and molecular mechanisms underlying a given disease condition offers a novel approach to fight disease and restore health, ushering in modern chronomedicine.