Dimethyl sulfoxide (DMSO) is an important solvent that is widely used in industry and medical studies, as well as in the study of aging, in which it is used as a negative control for lifespan assays; however, our data showed that 0.5% and 2% DMSO extended the lifespan of Caenorhabditis elegans by 24.4% and 23.0% (the first trial), respectively. Treatment with 0.5% DMSO did not affect the progeny number or the lifespan of C. elegans under thermal stress. Using real time reverse transcription polymerase chain reaction (RTPCR), we found that the expression levels of hsp-16.2, hsp-70, lys-7, old-1, and sod-5 were enhanced by 2.5, 2.9, 1.3, 2.3, and 4.5-fold, respectively, after treatment with 0.5% DMSO. This suggests that these genes downstream of DAF-16 might function in the lifespan extension properties of DMSO. Using the transgenic strain lys-7::GFP, we found that treatment with 0.5% DMSO also caused expression levels of lys-7 increased by 1.5-fold. Genetic analysis using mutants of aging-related genes showed that lifespan extension in C elegans by DMSO was dependent on sir-2.1 and daf-16 but not eat-2 or hsf-1. In summary, we report the function and the putative mechanism of DMSO in lifespan extension of C elegans. This study draws attention to using DMSO as a solvent when conducting aging studies. (c) 2010 Elsevier Inc. All rights reserved.