生物時計による骨格筋機能制御

抄録

Circadian rhythms are approximate 24-hour biological cycles that synchronize the timing of an organism's behavior and physiology to daily environmental changes. This endogenously generated temporal coordination has been experimentally shown to provide an adaptive advantage by enhancing an organism's ability to anticipate daily changes in light, temperature and humidity etc. The molecular mechanism responsible for generating circadian rhythms is a highly conserved gene regulatory network composed of transcriptional-translational feedback loops referred to as the Core-Clock. In mammals, the proteins encoded by Core-Clock genes, Bmal1 and Clock, dimerize to drive transcription of Period and Cryptochrome and the protein products of these genes down-regulate BMAL1 and CLOCK function. BMAL1:CLOCK heterodimers also transcriptionally regulate a group of genes referred to as clock-controlled genes which are believed to be necessary for maintenance of normal cell physiology.
In this review, the bases of the circadian rhythms regulation in the central/peripheral tissues are discussed. Particular emphasis has been placed on understanding of circadian regulation of skeletal muscle structure and function. Recently, tissue-specific circadian transcriptome including MyoD1, which is the well-known myogenic lineage regulator, were identified in skeletal muscle. Understanding the molecular, physiological and biophysical mechanisms through which the Core-Clock genes and the tissue-specific circadian transcriptome maintain skeletal muscle structure/function is of great significance with broad translational implications associated with chronic disease, metabolic failure and disuse.