Abstract :
With a long history of application in Chinese traditional medicine, berberine (BBR) was reported to exhibit healthspan-extending properties in some age-related diseases, such as type 2 diabetes and atherosclerosis. However, the antiaging mechanism of BBR is not completely clear. By means of hydrogen peroxide- ([H.sub.2][O.sub.2]-) induced premature cellular senescence model, we found that a low-concentration preconditioning of BBR could resist premature senescence in human diploid fibroblasts (HDFs) measured by senescence-associated [beta]-galactosidase (SA-[beta]-gal), accompanied by a decrease in loss of mitochondrial membrane potential and production of intracellular reactive oxygen species (ROS). Moreover, the low- concentration preconditioning of BBR could make cells less susceptible to subsequent [H.sub.2][O.sub.2]-induced cell cycle arrest and growth inhibition. Experimental results further showed that the low concentration of BBR could induce a slight increase of ROS and upregulate the expression level of sirtuin 1 (SIRT1), an important longevity regulator. [H.sub.2][O.sub.2]-induced activation of checkpoint kinase 2 (Chk2) was significantly attenuated after the preconditioning of BBR. The present findings implied that the low- concentration preconditioning of BBR could have a mitohormetic effect against cellular senescence triggered by oxidative stress in some age-related diseases through the regulation of SIRT1.