エイジングと生体リズム

Summary 　Rhythmic change of the internal milieu is a fundamental principle in all living organisms. Human is not exceptional, and a variety of physiological and pathological symptoms show the daily rhythms. Recent advances of molecular dissection of circadian rhythms have established the concept that physiologically relevant circadian time is generated at the level of transcription-(post) translation feedback loop of clock genes, which machinery can be found in most cells throughout the body. Similarly, cellular senescence is a limited ability of primary human cells to divide when cultured in vitro and is accompanied by a specific set of phenotypic changes in morphology and gene expression and functions, which is speculated to occur in human aging and age-associated diseases. Increasing evidences suggest that disruption of the circadian clock system is associated with various pathogenic conditions and may be highly relevant to aging processes, and age-associated diseases including metabolic syndrome, hypertension, and cancer. Completely arrhythmic Cry-null mice shows the salt-sensitive hypertension, and chronic jeglag increases mortality rates in aged mice, not in young mice. Since decreases of oscillatory ability in clock genes are associated with cellular senescence, the regulation of clock gene expression may be a novel strategy for the treatment of age-associated phenomena.