Accumulative evidence suggests that species life-span is determined, at least in part, genetically. Recent cloning works using yeast (Saccharomyces cerevisiae) and worms (Caenorhabditis elegans) revealed several potential candidate genes, e.g. SIR4, a transcriptional silencing factor, and age-1, a putative signal transduction molecule, respectively, that may be involved in determining and/or regulating species life-span in lower organisms. It is, however, not clear yet whether mammalian homologs of these genes are also relevant to controlling longevity in higher organisms. In mice and humans several silencing factors are essential for cell-type specific gene expression. A variety of signal transducing molecules are also known to play important roles in mammals. I will briefly summarize recent progress in molecular genetic studies on such longevity-related genes, and discuss these results with our recent findings on a neural-selective silencing factor and a neural-specific signaling molecule that are important for functioning of the nervous system.