Nakahata Yasukazu, Bessho Yasumasa
Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Biomed Res Int. 2016;2016:3208429. doi: 10.1155/2016/3208429. Epub 2016 Dec 5.
Gene expression is known to be a stochastic phenomenon. The stochastic gene expression rate is thought to be altered by topological change of chromosome and/or by chromatin modifications such as acetylation and methylation. Changes in mechanical properties of chromosome/chromatin by soluble factors, mechanical stresses from the environment, or metabolites determine cell fate, regulate cellular functions, or maintain cellular homeostasis. Circadian clock, which drives the expression of thousands of genes with 24-hour rhythmicity, has been known to be indispensable for maintaining cellular functions/homeostasis. During the last decade, it has been demonstrated that chromatin also undergoes modifications with 24-hour rhythmicity and facilitates the fine-tuning of circadian gene expression patterns. In this review, we cover data which suggests that chromatin structure changes in a circadian manner and that NAD is the key metabolite for circadian chromatin remodeling. Furthermore, we discuss the relationship among circadian clock, NAD metabolism, and aging/age-related diseases. In addition, the interventions of NAD metabolism for the prevention and treatment of aging and age-related diseases are also discussed.
基因表达是一种随机现象。随机基因表达率被认为会因染色体的拓扑变化和/或染色质修饰（如乙酰化和甲基化）而改变。可溶性因子、环境机械应力或代谢产物引起的染色体/染色质机械性质变化决定细胞命运、调节细胞功能或维持细胞内稳态。昼夜节律时钟驱动数千个基因以24小时节律表达，已知其对于维持细胞功能/内稳态不可或缺。在过去十年中，已证明染色质也以24小时节律进行修饰，并促进昼夜节律基因表达模式的微调。在这篇综述中，我们涵盖的数据表明染色质结构以昼夜节律的方式变化，并且NAD是昼夜节律染色质重塑的关键代谢产物。此外，我们讨论了昼夜节律时钟、NAD代谢与衰老/年龄相关疾病之间的关系。此外，还讨论了NAD代谢干预对衰老和年龄相关疾病的预防和治疗作用。
