Calorie-restricted diets are known to extend lifespans of model animals, including nematodes, flies, mice and monkeys. It is believed that calorie-restricted diets delay the onset of aging-associated diseases such as diabetes, cancer and Alzheimer's disease, and also prolong human longevity. However, in reality, it is difficult to continue calorie-restricted diets for a long period of time. Therefore, the development of calorie restriction mimetics (CRMs) that have similar effects as calorie-restricted diets is of great interest. Our preliminary study showed that the rare sugar D-psicose, a stereoisomer of D-fructose, extended the lifespan of Caenorhabditis elegans. The findings suggest that D-psicose serves as a CRM in C. elegans. The extension of C. elegans lifespan under calorie-restricted diet conditions is thought to be dependent on the induction of oxidative stress-related proteins, including Cu/Zn-superoxide dismutase (SOD), Mn-SOD and catalase regulated by the insulin/IGF-I signaling pathway. We aimed to elucidate the molecular mechanism of the lifespan extension by D-psicose. Wild-type C. elegans N2 was used in this study. Treatment of worms with 28 mM D-psicose increased mean lifespan of N2 by ca. 20% (control: 20.9 days; D-psicose: 25.1days). Using Quantitative real-time RT-PCR, we found that the mRNA expression levels of mitochondrial Mn-SOD (
sod-3), cytosolic catalase (
ctl-1) and peroxisomal catalase (
ctl-2) were enhanced by 1.4, 1.5 and 1.6-fold, respectively, after treatment of D-psicose. In contrast, expression of cytosolic Cu/Zn-SOD (
sod-5) was unaffected by 28mM D-psicose treatment. Total SOD and catalase enzyme activities in N2 with 28 mM D-psicose treatment were increased by 1.4 and 2.1-fold, respectively. D-psicose was thought to extend the lifespan of C. elegans by increasing the oxidative-stress resistance of the nematode. These results indicate that D-psicose is a candidate CRM.