Advanced glycation end-product(s) (AGE) are formed in biological systems when reducing sugars react with amino groups on proteins. Long-lived proteins such as collagen and lens crystallins are known to be susceptible to AGE modification and may play a major role in the development of diabetes and other age-related pathologies. It has been previously suggested that AGE formation might affect the lifespan of experimental animals. Our study is the first to examine the effect of AGE accumulation on the life span of an organism, Drosophila melanogaster. We found that Drosophila melanogaster maintained at 24 degrees C accumulate significant AGE over their lifespan. Young flies (10 days old) had 44% less AGE than senescent flies (75 days old). We were able to reduce AGE accumulation in Drosophila melanogaster by raising the flies on a medium containing a known AGE inhibitor, aminoguanidine HCl. Reduction of AGE in flies failed to increase their mean lifespan, and high concentrations (40 mM) reduced the mean life span, which suggests that aminoguanidine is toxic at levels near those required for inhibition of AGE formation. However, the common fruit fly, Drosophila melanogaster, provides a simple model system to study the age-dependent accumulation of glycated proteins and their inhibition by novel compounds.