DECIPHERING THE MOLECULAR DYNAMICS INVOLVED IN THE INDUCTION OF SENESCENCE IN CELLS EXPOSED TO SUBTOXIC LEVELS OF OXIDATIVE STRESS

Abstract

CELLULAR SENESCENCE IS A STATE OF IRREVERSIBLE CELL CYCLE ARREST THAT PREVENT THE DELETERIOUS CELLS FROM FURTHER DIVISION EVENTUALLY LEADING TO SUPPRESSION OF CANCER AND PROMOTION OF AGING. HOWEVER, THE MOLECULAR MECHANISMS AND THE EXACT FUNCTIONAL ROLE OF SENESCENCE ARE NOT CLEAR. IN THIS STUDY, WE HAVE ADDRESSED THE IMPORTANT KNOWLEDGE GAPS IN THE INITIATION, DECISION AND DEEPENING OF SENESCENCE PROCESSES BY TRIGGERING THE CELLS WITH SUBTOXIC OXIDATIVE STRESS. AFTER 1 H OF HYDROGEN PEROXIDE EXPOSURE TO THE CELLS, WE OBSERVED THE FIRST PHASE OF DNA DAMAGE (FPDD), WHICH WAS TRANSIENT AND REPAIRED QUICKLY. FOLLOWING 12 H OF THE INITIAL TRIGGER WITHIN THE FIRST CELL CYCLE, WE NOTICED A SECOND PHASE OF DNA DAMAGE (SPDD), WHICH SUSTAINED FOR A LONGER TIME. THERE WAS ROS\RNS INDUCTION AT THE SAME TIME AS SPDD, BUT INTERESTINGLY, WE FOUND THAT ROS\RNS WAS NOT THE CAUSE BUT THE CONSEQUENCE OF SPDD. WE ALSO FOUND THAT THE FORMATION OF SPDD WAS MEDIATED BY REPLICATIVE STRESS. AFTER ITS INDUCTIO