Ouroboros On p53 Decline and Late-Life Cancer
From Chris Patil Ouroboros: "If p53 were to somehow go AWOL in a cell, it would bode poorly for cancer prevention. Lacking this critical checkpoint control, genetically damaged cells could go on cycling, perhaps developing additional genomic changes that further encourage unrestricted growth, and eventually becoming frankly neoplastic. A recent study from Arnie Levine's lab shows that the p53 response to one form of genotoxic stress (ionizing radiation) becomes less efficient [in] old mice. If this finding is general to other humans, it could partially explain why the risk of tumors increases exponentially with age. ... I wonder whether a contributing factor might be adaptation of the signaling pathways involved. Signaling pathways almost always involve some negative feedback; among other things, this serves to prevent inappropriate activation of a pathway in response to a low baseline level of stimulus, to preserve the dynamic range of the system and reset the threshold so that it can be triggered only by really noteworthy events." Patil goes on to suggest an off the cuff theory as to how declines in p53 - and increased propensity to cancer - might operate, some tests of the hypothesis, and how the system might be reset if true.
Link: http://ouroboros.wordpress.com/2007/12/13/p53-decline-in-old-age-a-cause-of-late-life-cancer/