Telomeres are multifunctional elements that protect chromosomal ends. Telomere length affects lifespan and stress resistance. In our previous report, we found that the increase of telomere length extended organismic lifespan in Caenorhabditis elegans. To investigate the effect of the telomere length on organismic lifespan at the global gene expression level, we performed microarray experiments using mRNA from long telomere-containing worms. We identified genes that showed significant difference in transcript levels from long telomere-containing worms. We examined the expression patterns of these genes and measured lifespan of the worms over-expressing each of the up-regulated genes. Most up-regulated genes, when over-expressed, extended lifespan of C. elegans. In particular, over-expression of rnh-1.3 in the intestine extended lifespan in the daf-16-dependent manner and increased stress resistance. Interestingly, genes up-regulated in long telomeric worms partially overlapped with the genes whose transcription was increased by the rde-3 mutations, and the over-expression of each of these genes also extended the longevity of worms, raising the possibility that the telomere effect may involve molecular players shared with the RNAi machinery. (C) 2010 Elsevier Inc. All rights reserved.