Senescence as a conundrum of life and death
Aging is the major risk factor for many chronic diseases accounting for the bulk of morbidity, mortality, and health costs in the world. There is significant evidence that the accumulation of senescent cells can drive many phenotypes and pathologies associated with aging. How senescence mechanistically or dynamically contributes to the aging process remains largely unknown. To address the role of senescence in aging, we successfully targeted the endogenous p16 locus (knock- in) with two types of Cre systems without disrupting either p16Ink4a or p19Arf genes. First, we introduced a constitutively active Cre. In this case, once generated, the senescent cells are labeled or eliminated depending on a reporter line used (Rosa26-mTmG (tracer line) or Rosa26-DTA (ablator line)). In a second mouse line, we introduced a Tamoxifen (TAM)-inducible version of Cre, Cre-ERT2, so that injection of tamoxifen results in a temporal labeling (or elimination) of senescent cells. The analysis of these 2 mouse lines in the aging mice and in cancer will be presented.
Institute for Research on Cancer and Aging, IRCAN Nice
Domain 2 - UMR 3244 - Dynamics of genetic Information