成纤维细胞端粒酶重建对生物节律的调控

为探讨衰老对生物节律调控的分子机理,以青龄、衰老和端粒酶重建的皮肤成纤维细胞作为细胞模型,检测节律基因Per2,BMAL1和Clock表达.衰老细胞中节律基因表达受损,端粒酶重建细胞恢复了节律基因的节律性表达,提示端粒酶重建细胞可望用于衰老细胞的替代治疗.

Telomerase Reconstitution in Fibroblasts Regulates Cell Circadian Rhythm

The entrainment of the circadian signals to external or suprachiasmatic nucleus stimulation in the peripheral clocks is essen-tial for maintaining the normal function of human body. However, aging will disrupt the entrainment of peripheral circadian rhythms, thus lead-ing to some age associated diseases. Up till now, little is known about the modification of the oscillatory rhythms in aged cells. A recent report showed that cell senescence in vascular human smooth muscle cells (HSMCs) altered circadian rhythms by a disregulatiou of rhythmic genes expression. Furthermore, this alteration could be reversed by telomerase roconstitution. To test whether telomerase reconstitution can restore disrupted circadian rhythm in other types of senescent cells, we used fibroblasts as cell models to profoundly investigate the relationship be-tween cell senescence and circadian rhythm modulation. We found that the response of rhythmic genes expression to serum stimulation was markedly attenuated in senescent fibroblasts, and telomerase reconstituted fibroblasts reset the circadian oscillation of rhythmic genes expres-siou. These findings suggested that telomerase reconstitution might be a good way to reset entrainment of peripheral circadian rhythms disrupt-ed in senescent tissues.