The accumulation of senescent cells induces age-related dysfunction in various organs,and the selective clearance of senescent cells is a potential approach for treating age-related diseases.Hence,identifying natural ...The accumulation of senescent cells induces age-related dysfunction in various organs,and the selective clearance of senescent cells is a potential approach for treating age-related diseases.Hence,identifying natural foods that provide senolytic benefits is important because they may serve as a preventative measure and an alternative to pharmaceutical interventions for aging that mitigates the potential side effects associated with drug-based approaches.In this study,we investigated the senolytic activity of ethanol extracts derived from Agrimonia pilosa Ledeb(APL-E)and agrimol B,an active component of the plant,in doxorubicin-induced senescent WI38 cells.APL-E and agrimol B decreased senescence-associated-β-galactosidase(SA-β-gal)-positive senescent WI38 cells in a concentration-dependent manner.Annexin V staining revealed that APL-E and agrimol B caused apoptosis in senescent cells.To investigate the effect of APL-E on senolytic activity in vivo,aged male C57BL/6J mice were fed APL-E for 3 months.SA-β-gal staining revealed significantly decreased senescent cells in the liver and kidney of APL-E-fed aged mice.The expression levels of senescence-associated secretory phenotype factors Il1β,Ccl2,and Cxcl9 were also decreased in the livers and kidneys of APE-fed mice.The number of senescent CD8^(+)T cells in the blood decreased in APL-E-fed aged mice.Furthermore,APL-E-fed mice showed improvement in aging-induced immune senescence,marked by increased naïve CD8^(+)T cells and decreased memory CD8^(+)T cells.This study provides evidence of the novel senolytic activity of APL-E and agrimol B and suggests their application as preventatives against various age-related disorders.展开更多
文摘The accumulation of senescent cells induces age-related dysfunction in various organs,and the selective clearance of senescent cells is a potential approach for treating age-related diseases.Hence,identifying natural foods that provide senolytic benefits is important because they may serve as a preventative measure and an alternative to pharmaceutical interventions for aging that mitigates the potential side effects associated with drug-based approaches.In this study,we investigated the senolytic activity of ethanol extracts derived from Agrimonia pilosa Ledeb(APL-E)and agrimol B,an active component of the plant,in doxorubicin-induced senescent WI38 cells.APL-E and agrimol B decreased senescence-associated-β-galactosidase(SA-β-gal)-positive senescent WI38 cells in a concentration-dependent manner.Annexin V staining revealed that APL-E and agrimol B caused apoptosis in senescent cells.To investigate the effect of APL-E on senolytic activity in vivo,aged male C57BL/6J mice were fed APL-E for 3 months.SA-β-gal staining revealed significantly decreased senescent cells in the liver and kidney of APL-E-fed aged mice.The expression levels of senescence-associated secretory phenotype factors Il1β,Ccl2,and Cxcl9 were also decreased in the livers and kidneys of APE-fed mice.The number of senescent CD8^(+)T cells in the blood decreased in APL-E-fed aged mice.Furthermore,APL-E-fed mice showed improvement in aging-induced immune senescence,marked by increased naïve CD8^(+)T cells and decreased memory CD8^(+)T cells.This study provides evidence of the novel senolytic activity of APL-E and agrimol B and suggests their application as preventatives against various age-related disorders.
