Liu Fang, Chang Hung-Chun
Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
University of Chinese Academy of Sciences, Shanghai, 200031, China.
Protein Cell. 2017 Jul;8(7):477-488. doi: 10.1007/s13238-016-0366-2. Epub 2017 Jan 20.
Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold self-sustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurodegenerative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resembled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.
昼夜节律协调生物体中的生化和生理过程以响应昼夜循环。在哺乳动物中，几乎所有细胞都拥有自我维持的生物钟，同时以分级方式将内在节律与全身变化相耦合。下丘脑的视交叉上核（SCN）作为主起搏器，根据光周期启动每日同步，进而通过包括内分泌节律和代谢周期在内的各种信号传递来确定外周细胞时钟的相位。随着年龄增长，昼夜节律失调会导致外周代谢病理和伴有睡眠症状的中枢神经退行性疾病，而模式生物中昼夜节律基因的基因消融类似于与衰老相关的特征。值得注意的是，许多研究已将长寿营养感应途径与调节生物钟联系起来。连接营养感应途径和生物钟的治疗策略可能是对抗衰老的合理设计。
