Deficiency of the circadian clock transcriptional factor BMAL1 results in the 
development of premature aging in mice. In agreement with the accelerated aging 
phenotype, we observed an increase in the number of senescent cells in different 
tissues (lungs, liver and spleen) of Bmal1(-/-) mice, which suggests the 
important role of BMAL1 in the control of senescence in vivo. However, no 
difference in the rate of proliferation and senescence between primary 
fibroblasts isolated from wild-type and Bmal1(-/-) mice has been detected, 
suggesting that BMAL1 does not play a significant role in replicative senescence 
in vitro. BMAL1 deficient fibroblasts had an increased sensitivity to hydrogen 
peroxide treatment, and reduced sensitivity to DNA damaging anticancer drugs 
etoposide and daunorubicin. Increased sensitivity of Bmal1(-/-) cells to 
oxidative stress was p53 independent and correlated with the disrupted 
regulation of reactive oxygen species (ROS) homeostasis in BMAL1 deficient 
cells: indeed, circadian oscillations of ROS level can be induced in wild-type 
but not in Bmal1(-/-) cells. We propose that BMAL1 is important for the 
regulation of oxidative stress and DNA damage responses, while deregulation of 
these processes upon BMAL1 deficiency leads to development of stress induced 
senescence in vivo.