Is DNA damage indispensable for stress-induced senescence?

Cellular senescence is a fundamental trait of many eukaryotic organisms. Senescent cells participate both in the developmental program and in normal ageing and age-related diseases. Senescence of proliferation-prone cells is a state of permanent cell cycle arrest accompanied by metabolic activity manifested by high secretion levels of numerous factors, including pro-inflammatory ones. It seems that cell senescence is a stress response. There are many intrinsic and extrinsic stress inducers which can elicit cell senescence. Generally accepted are those causing DNA double strand breaks (DSBs), which trigger permanent activation of DNA damage response (DDR) considered as a hallmark and a cause of cell senescence. In this review we discuss the possibility that cell senescence can be acquired in the absence of DDR or following DDR in the absence of DNA damage. Any scenario seems possible, based on data obtained by many researchers including ourselves, but it should be emphasized that unrepaired DSBs are a well-recognized trigger of senescence.