SummaryHuman diploid fibroblasts have the capacity to complete a finite number of cell divisions before entering a state of replicative senescence characterized by growth arrest, changes in morphology, and altered gene expression. Herein, we report that interaction with extracellular matrix (ECM) from young cells is sufficient to restore aged, senescent cells to an apparently youthful state. The identity of the restored cells as having been derived from senescent cells has been confirmed by a variety of methods, including time lapse live cell imaging and DNA finger print analysis. In addition to cell morphology, phenotypic restoration was assessed by resumption of proliferative potential, growth factor responsiveness, reduction of intracellular reactive oxygen species levels, recovery of mitochondrial membrane potential, and increased telomere length. Mechanistically, we find that both Ku and SIRT1 are induced during restoration and are required for senescent cells to return to a youthful phenotype. These observations demonstrate that human cellular senescence is profoundly influenced by cues from the ECM, and that senescent cell plasticity is much greater than that was previously believed to be the case.

PurposeThe purposes of this study were to investigate the effect of cyclophosphamide (CYP)-induced inflammatory cystitis on caveolin 1 in rat urinary bladder and to determine the role of these molecules in the bladder dysfunction that occurs in inflammatory change in rat urinary bladder.MethodsFemale Sprague-Dawley rats were divided into control (n=30) and experimental (n=30) groups. Cystitis in experimental group was induced by intraperitoneal injection of CYP (200 mg/kg). The control group underwent an intraperitoneal saline injection. After 3 days, urodynamic studies were done to measure the contraction interval and contraction pressure. The expression and cellular localization of caveolin 1 were determined by Western blot and immunofluorescent study in rat urinary bladder.ResultsIn cystometrograms, the contraction interval (minute) was significantly increased in the CYP-induced cystitis rats (15.8±1.5) than in the control group (6.3±0.5) (P<0.05). Conversely, the average contraction pressure (mmHg) was significantly higher in the CYP-induced cystitis rats (15.6±1.7) than in the control group (11.3±0.5) (P<0.05). Caveolin 1 was expressed in the capillaries, arteriols and venules. The protein expression of caveolin 1 was significantly decreased in the CYP-induced cystitis rats (P<0.05).ConclusionsInflammatory change of urinary bladder maybe causes a significant change in the expression of caveolin 1. These findings suggest that caveolin 1 might have a functional role in the bladder dysfunction related with cystitis in rat urinary bladder.