#5461 KIDNEY TUBULE POLYPLOIDIZATION DURING PHYSIOLOGIC AGEING IN MICE

Abstract Background and Aims The aged population is constantly increasing, kidney-aging a risk factor for both acute kidney injury (AKI) chronic disease (CKD). Accordingly, CKD major global health problem with an increasing prevalence in older population. Therefore, there urgent need to understand the age-related mechanisms underpinning development during ageing. Recent findings contributed clarify cellular molecular underlying progression, posing tubular cells (TC) at center of this process. In regard, we have demonstrated that polyploidization TC promotes fibrosis, its progression long run. Here, aimed investigate physiologic ageing mice. Method To ageing, took advantage inducible Pax8/FUCCI2aR these mice, FUCCI2aR reporter expressed by all after doxycycline hyclate induction. Mice were sacrificed analyzed 2, 5, 11 20 months age. By combining DNA content detection fluorescent proteins, FACS analysis shows diploid (2C), tetraploid (4C) octaploid or greater (≥8C) TC. Single cell RNA-sequencing (scRNA-seq) was performed on mouse kidneys 2 age dissect transcriptomic profile polyploid interrogate putative altered signaling pathways. Renal function parameters assessed before sacrifice. Kidneys senescence interstitial fibrosis Results Genetic single-cell approaches mice used showed progressive increase starting from 5 ScRNA-seq revealed characterized polyploidy regulators, p21 expression, accumulation damage acquiring senescent/fibrotic markers, demonstrating rather than accumulate acquire senescent/pro-fibrotic state vivo. accordance TC, developed marked senescent phenotype decline renal Collectively, results suggest potential trigger Conclusion This study demonstrates polyploidization, which associated