Biomedical effects of circadian rhythm disturbances

Abstract

Circadian rhythms are biological processes that recur on a daily basis and exist to appropriately organize physiology, metabolism, and behavior relative to the 24-h light/dark cycle created by the rotation of the Earth. These rhythms are controlled by a genetically encoded molecular clock active in most, if not all, cells in the body. In mammals, these cell-autonomous oscillators are regulated and synchronized by the master clock in the suprachiasmatic nucleus (SCN) of the hypothalamus through a variety of direct and indirect pathways. The circadian timekeeping system imposes integrated temporal organization to ongoing biochemical and physiological processes throughout the body, ensuring optimal functioning in the context of repeated environmental changes driven by the solar cycle. It is well known that shift workers are at greater risk for development of a large number of chronic diseases and recent experimental evidence has shown that disruption of circadian organization leads to physiological impairments and dysfunction that are relevant for disease development and pathology. In particular, circadian disturbances yield metabolic derangements capable of predisposing individuals to diabetes, obesity, gastrointestinal and cardiovascular disease, and to disease states which have been linked to increases in risk for various cancers. In addition, the molecular circadian machinery has been linked to regulators of the cell cycle and other prominent pathways involved in cancer, including DNA repair and apoptosis. An understanding of the circadian timekeeping system and recognition of its fundamental role in temporal organization of biochemical pathways and physiological processes enables a framework upon which the concept of time on a 24-h basis can be applied to translational research and brought into the realm of clinical medicine in order to improve diagnostics, therapeutics and, ultimately, patient outcomes.