#3612 STING IS INVOLVED IN THE CELLULAR SENESCENCE PROCESS ASSOCIATED WITH RENAL AGING

Abstract Background and Aims Cellular senescence is an adaptative process in response to damage or stress. It consists of a cell-cycle-arrest (CCA) alternatively the programmed cell death process, which necessary for regeneration damaged tissues. However, permanent promotes aberrant inflammatory associated chronic diseases, fibrosis aging. One mechanisms triggers cellular DNA (DDR) activation, that leads emergence senescence-associated secretory phenotype (SASP), inflammation fibrosis. Sting detection protein pathogenic derived from genotoxic environmental stresses, starting innate immune inflammation. A deregulated DDR thus itself, are also able activate Sting. Nevertheless, role renal aging unknown fact. The aim this study evaluate STING aging-associated pathophysiological changes kidney. Method Studies were carried out C57BL76 mice (wild type mice) with deficient gene (KO-Sting), different ages: 3 (young) 18 (aged) months. Renal function parameters, histology markers kidney damage, activation presence absence studied. Results month presented dysfunction was not observed KO-Sting same age. Interestingly, months wild-type showed pathway, characterized by increased transcriptional levels Ifit1, Oasl2, Usp19 Mx2. Moreover, pathway mechanisms, including elevated expression SASP components, such as Ccl2, Ccn2, Il1β, Il6, Pai1 Tgf-β. Importantly, KO months, activated (no increase ɣH2AX) cycle arrest induced, determined p21 p16 markers. In addition, SAPS remained at basal aged mice. Klotho downregulated all 18-month-old mice, wild Conclusion conclusion, these findings suggest prevents age-related independent manner murine experimental model.