突触功能必需基因参与线虫衰老的调控(英文)

目的鉴定参与线虫衰老的神经内分泌调控的新基因。方法鉴于神经系统在衰老调控中的重要作用,通过寿命分析和脂褐质自发荧光的检测,从编码突触蛋白的遗传位点中筛选参与衰老调控的基因。我们还进一步检查了这些遗传位点相应的突变体的永久性幼虫形成情况,探讨它们是否可能受胰岛素样信号通路的调控。结果遗传位点 unc-10,syd-2,hlb-1,dlk-1,mkk-4,scd-2,snb-1,ric-4,nrx-1,unc-13,sbt-1,unc-64 可能参与线虫衰老的调控。而且在衰老的调控中,unc-10,syd-2,hlb-1,dlk-1,mkk-4,scd-2,snb-1,ric-4,nrx-1 的功能可能与unc-13,sbt-1,unc-64相反。肠道脂褐质自发荧光的检测进一步证明了筛选出的各基因对应突变体的长寿或短寿表型,是由减慢或缩短的组织衰老所致。在筛选出的基因中,syd-2,hlb-1,mkk-4,scd-2,snb-1,ric-4,unc-64 也参与了永久性幼虫形成的调控。另外,daf-2突变增强了syd-2和hlb-1的表达,降低了mkk-4,nrx-1,ric-4,sbt-1,rpm-1,unc-10,dlk-1,unc-13 的表达。daf-16突变提高了syd-2和 hlb-1 的表达,降低了mkk-4,nrx-1,sbt-1,rpm-1,unc-10,dlk-1,unc-13 的表达. 结论突触功能可能在个体寿命和永久性幼虫形成的调控机制中具有重要的作用。

Involvement of genes required for synaptic function in aging control in C.elegans

Objective To identify new genes required for neurosecretory control of aging in C. elegans. Methods In vi ew of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway. Results The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4, nrx-1, unc-13 , sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10 , syd-2 , hlb-1, dlk-1,mkk-4,scd-2,snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13,sbt-1 and unc-64 . The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2,hlb-1,mkk -4,scd-2,snb-1,ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1,and negatively regulated the expression of mkk-4,nrx-1,ric-4,sbt-1, rpm-1,unc-10 , dlk -1 and unc-13.The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4,nrx-1,sbt-1,rpm-1,unc-10,dlk-1and unc-13.Conclusion These data suggest the possibly important status of the synaptic transmission to the animal's life-span control machinery, as well as the dauer formation control.