Senotherapeutic effect of Agrimonia pilosa Ledeb. in targeting senescent cells in naturally aged mice

Abstract

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.