Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts.
The synchronization of the circadian signals to external or suprachiasmatic nucleus stimulation in the peripheral clocks is essential for maintaining the usual function of human body. However, aging will disrupt the synchronization of peripheral circadian rhythms, thus leading to some age-associated diseases. Up to 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 dysregulation of rhythmic gene expression. Furthermore, this alteration could be reversed by telomerase reconstitution. 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 between cell senescence and circadian rhythm modulation. We found that the response of rhythmic gene expression to serum stimulation was markedly attenuated in senescent fibroblasts, telomerase-reconstituted fibroblasts reset the circadian oscillation of rhythmic gene expression, and the activation of pERK-CREB and p38-CREB pathways might be involved in the circadian rhythm resetting. These findings suggested that telomerase reconstitution might be a good way to reset synchronization of peripheral circadian rhythms disrupted in senescent tissues.
Qu
Yi
Y
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Mao
Meng
M
Li
Xihong
X
Liu
Yanyou
Y
Ding
Jianmin
J
Jiang
Zhou
Z
Wan
Chaomin
C
Zhang
Lin
L
Wang
Zhengrong
Z
Mu
Dezhi
D
D016922:Cellular Senescence; D002648:Child; D002940:Circadian Rhythm / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D044967:Serum; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D020928:Mitogen-Activated Protein Kinases; D019098:Telomerase; D001616:beta-Galactosidase