A C-terminal truncated mutation of spr-3 gene extends lifespan in Caenorhabditis elegans

The lifespan of Caenorhabditis elegans is determined by various genetic and environmental factors. In this paper, spr-3, a C. elegans homologous gene of the mammalian neural restrictive silencing factor （NRSF/REST）, is reported to be an important gene regulating lifespan of C. elegans. A deletion mutation ofspr-3, spr-3（ok2525）, or RNAi inhibition of spr-3 expression led to the short lifespan phenotype in C. elegans. However, a nonsense mutation of spr-3, spr-3（by108）, increased the lifespan by 26% when compared with that of wild-type nematode. The spr-3（byl08） also showed increased resistance to environmental stress. The spr-3（byl08） mutated gene encodes a C-terminal truncated protein with a structure comparable with the REST4, a splice variant of the NRSF/REST in mammalian. The long lifespan phenotype of spr-3（byl08） mutant is confirmed as a gain of function and dependent on normal functions of daf-16 and glp-1. The lifespan of the spr-3（byl08） can be syner- gistically enhanced by inducing a mutation in daf-2. Quantitative polymerase chain reaction results showed that the expression of daf-16 as well as its target gene sod-3, mtl- 1, and sip-1 was up-regulated in the spr-3（byl08） mutant. These results would be helpful to further understand the complex function of NRSF/REST gene in mammalian, especially in the aging process and longevity determination.