Bmal1-deficient mouse fibroblast cells do not provide premature cellular senescence in vitro

ABSTRACT

Bmal1 is a core circadian clock gene. Bmal1^−/− mice show disruption of the clock and premature aging phenotypes with a short lifespan. However, little is known whether disruption of Bmal1 leads to premature aging at cellular level. Here, we established primary mouse embryonic fibroblast (MEF) cells derived from Bmal1^−/− mice and investigated its effects on cellular senescence. Unexpectedly, Bmal1^−/− primary MEFs that showed disrupted circadian oscillation underwent neither premature replicative nor stress-induced cellular senescence. Our results therefore uncover that Bmal1 is not required for in vitro cellular senescence, suggesting that circadian clock does not control in vitro cellular senescence.

KEYWORDS:

• cellular senescence
• circadian clock
• Bmal1

Acknowledgments

This work was supported, in part, by The Uehara Memorial Foundation, and The Asahi Glass Foundation. We thank R. Ahmed and Dr. S. Sahar for their critical comments on the manuscript.

Declaration of Interest Statement

The authors report no conflicts of interest.

Funding

This work was supported by JSPS KAKENHI [grant number JP23689013 to YN], [grant number JP26830074 to YN], and [grant number JP17K08569 to YN].