Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts

A Correction to this article is available

This article has been updated


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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Change history

  • 25 June 2020

    In the original article, Fig.��4b was published incorrectly in which four to five lanes in Pi-ERK and Pi-CREB panels look very similar to each other (Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts, Mol Cell Biochem, 2008, 313:11���18). Since this image was stored in The Experiment Center of the West China Second University Hospital, Sichuan University, which was dissoluted in 2012, the original data cannot be traced. Experiments were therefore redone to verify the result and the correct version of Fig.��4b is provided in this correction.


  1. 1.

    Halberg F (1983) Quo vadis basic and clinical chronobiology: promise for health maintenance. Am J Anat 168:543–594

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Monk TH (2005) Aging human circadian rhythms: conventional wisdom may not always be right. J Biol Rhythms 20:366–374

    PubMed  Article  Google Scholar 

  3. 3.

    Hofman MA (2000) The human circadian clock and aging. Chronobiol Int 17:245–259

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Hofman MA, Swaab DF (2006) Living by the clock: the circadian pacemaker in older people. Ageing Res Rev 5:33–51

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Yamazaki S, Straume M, Tei H et al (2002) Effects of aging on central and peripheral mammalian clocks. Proc Natl Acad Sci USA 99:10801–10806

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Kolker DE, Fukuyama H, Huang DS et al (2003) Aging alters circadian and light-induced expression of clock genes in golden hamsters. J Biol Rhythms 18:159–169

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Kunieda T, Minamino T, Katsuno T et al (2006) Cellular senescence impairs circadian expression of rhythmic genes in vitro and in vivo. Circ Res 98:532–539

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Xie HQ, Yang ZM, Qu Y (2002) Culture of human fibroblasts transfected by human telomerase reverse transcriptase eukaryotic expression plasmid pGRN145 and their biological characteristics in vitro. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 16:195–199

    PubMed  Google Scholar 

  9. 9.

    Maier AB, Westendorp RJ, Heemst DV (2007) β-Galactosidase activity as a biomarker of replicative senescence during the course of human fibroblast cultures. Ann N Y Acad Sci 1100:323–332

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Balsalobre A, Damiola F, Schibler U (1998) A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell 93:929–937

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Obrietan K, Impey S, Smith D et al (1999) Circadian regulation of cAMP response element-mediated gene expression in the suprachiasmatic nuclei. J Biol Chem 274:17748–17756

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Travnickova BZ, Cermakian N, Reppert SM et al (2002) Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity. Proc Natl Acad Sci USA 99:7728–7733

    Article  CAS  Google Scholar 

  13. 13.

    Fukada Y, Okano T (2002) Circadian clock system in the pineal gland. Mol Neurobiol 25:19–30

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Halberg F (1980) Chronobiology: methodological problems. Acta Med Romana 18:399–440

    Google Scholar 

  15. 15.

    McNamara P, Seo SP, Rudic RD et al (2001) Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock. Cell 105:877–889

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Nagoshi E, Saini C, Bauer C et al (2004) Circadian gene expression in individual fibroblasts: cell-autonomous and self-sustained oscillators pass time to daughter cells. Cell 19:693–705

    Article  Google Scholar 

  17. 17.

    Welsh DK, Yoo SH, Liu AC et al (2004) Bioluminescence imaging of individual fibroblasts reveals persistent, independently phased circadian rhythms of clock gene expression. Curr Biol 14:2289–2295

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Akashi M, Nishida E (2000) Involvement of the MAP kinase cascade in resetting of the mammalian circadian clock. Genes Dev 14:645–649

    PubMed  CAS  Google Scholar 

  19. 19.

    Dunlap JC (1999) Molecular bases for circadian clocks. Cell 96:271–290

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    King DP, Takahashi JS (2000) Molecular genetics of the circadian rhythms in mammals. Annu Rev Neurosci 23:712–742

    Article  Google Scholar 

  21. 21.

    Preitner N, Damiola F, Lopez-Molina L et al (2002) The orphan nuclear receptor REV-ERBα controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110:251–260

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Allada R, Emery P, Takahashi JS et al (2001) Stopping time: the genetics of fly and mouse circadian clocks. Annu Rev Neurosci 24:1091–1119

    PubMed  Article  CAS  Google Scholar 

Download references


This work was supported by the National Natural Science Foundation of China (No. 30570902 to Zhengrong Wang, Nos. 30570623 and 30770748 to Dezhi Mu) and Doctoral Program of Ministry of Education of China (No. 20050610094 to Yi Qu and No. 20070610092 to Dezhi Mu).

Author information



Corresponding authors

Correspondence to Zhengrong Wang or Dezhi Mu.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Qu, Y., Mao, M., Li, X. et al. Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts. Mol Cell Biochem 313, 11–18 (2008).

Download citation


  • Telomerase
  • Fibroblasts
  • Circadian rhythm
  • Rhythmic gene