Background The accumulation of free radicals and advanced glycation end products(AGEs)in cell plays a veryimportant role in replicative senescence.Aminoguanidine(AG)has potential antioxidant effects and decreases AGEl...Background The accumulation of free radicals and advanced glycation end products(AGEs)in cell plays a veryimportant role in replicative senescence.Aminoguanidine(AG)has potential antioxidant effects and decreases AGElevels.This study aimed to investigate its effect on replicative senescence in vitro.Methods The effects of aminoguanidine on morphology,replicative lifespan,cell growth and proliferation,AGEs,DNAdamage,DNA repair ability and telomere length were observed in human fetal lung diploid fibroblasts(2BS).Results Aminoguanidine maintained the non-senescent phenotype of 2BS cells even at late population doubling(PD)and increased cumulative population doublings by at least 17-21 PDs.Aminoguanidine also improved the potentials ofgrowth and proliferation of 2BS cells as detected by the MTT assay.The AGE levels of late PD cells grown from early PDin DMEM containing aminiguanidine decreased significantly compared with those of late PD control cells and were similarto those of young control cells.In addition,the cells pretreated with aminoguanidine had a significant reduction in DNAstrand breaks when they were exposed to 200 μmol/L H_2O_2 for 5 minutes which indicated that the compound had astrong potential to protect genomic DNA against oxidative stress.And most of the cells exposed to 100 μmol/L H_2O_2 hadmuch shorter comet tails and smaller tail areas after incubation with aminoguanidine-supplemented DMEM,whichindicated that the compound strongly improved the DNA repair abilities of 2BS cells.Moreover,PD55 cells grown fromPD28 in 2 mmol/L or 4 mmol/L aminoguanidine retain telomere lengths of 7.94 kb or 8.12 kb,which was 0.83 kb or 1.11kb longer than that of the control cells.Conclusion Aminoguanidine delays replicative senescence of 2BS cells and the senescence-delaying effect ofaminoguanidine appear to be due to its many biological properties including its potential for proliferation improvement,itsinhibitory effect of AGE formation,antioxidant effect,improvement of DNA repair ability and the slowdown of telomereshortening.展开更多
基金This work was-supported by the grants from the National Nature Science Foundation of China （No. 30672469） and Beijing Nature Science Foundation （No. 7062030）.
基金This work was supported by the grants from the National Natural Science Foundation of China(No.30672469)the Beijing Natural Science Foundation(No.7062030)
文摘Background The accumulation of free radicals and advanced glycation end products(AGEs)in cell plays a veryimportant role in replicative senescence.Aminoguanidine(AG)has potential antioxidant effects and decreases AGElevels.This study aimed to investigate its effect on replicative senescence in vitro.Methods The effects of aminoguanidine on morphology,replicative lifespan,cell growth and proliferation,AGEs,DNAdamage,DNA repair ability and telomere length were observed in human fetal lung diploid fibroblasts(2BS).Results Aminoguanidine maintained the non-senescent phenotype of 2BS cells even at late population doubling(PD)and increased cumulative population doublings by at least 17-21 PDs.Aminoguanidine also improved the potentials ofgrowth and proliferation of 2BS cells as detected by the MTT assay.The AGE levels of late PD cells grown from early PDin DMEM containing aminiguanidine decreased significantly compared with those of late PD control cells and were similarto those of young control cells.In addition,the cells pretreated with aminoguanidine had a significant reduction in DNAstrand breaks when they were exposed to 200 μmol/L H_2O_2 for 5 minutes which indicated that the compound had astrong potential to protect genomic DNA against oxidative stress.And most of the cells exposed to 100 μmol/L H_2O_2 hadmuch shorter comet tails and smaller tail areas after incubation with aminoguanidine-supplemented DMEM,whichindicated that the compound strongly improved the DNA repair abilities of 2BS cells.Moreover,PD55 cells grown fromPD28 in 2 mmol/L or 4 mmol/L aminoguanidine retain telomere lengths of 7.94 kb or 8.12 kb,which was 0.83 kb or 1.11kb longer than that of the control cells.Conclusion Aminoguanidine delays replicative senescence of 2BS cells and the senescence-delaying effect ofaminoguanidine appear to be due to its many biological properties including its potential for proliferation improvement,itsinhibitory effect of AGE formation,antioxidant effect,improvement of DNA repair ability and the slowdown of telomereshortening.
