RNAi Mediated Gene Disruption in Caenorhabditis Elegans

申请响应研究目标21“遗传学，行为，社会因素和老龄化”的NIA试点研究资助计划。 虽然导致衰老的机制最近已成为深入研究的主题，但衰老的多因素性质使得很难理清导致衰老的因素。确定衰老的因果机制的一个强有力的方法是研究基因突变或使用密集分析的模式生物延长寿命的操作，如线虫秀丽隐杆线虫。提出了一种鉴定影响长寿基因的新方法。elegans是使用RNA介导的干扰（RNAi）。RNAi通过使用靶向特定mRNA进行降解的双链RNA来沉默基因表达。RNAi已被证明是研究C.并已被用于确定数百个基因，影响长寿的C。优雅然而，为了提供对衰老过程的真正了解，对C。除了按时间顺序的寿命，线虫和衰老还必须测定其他生理功能的指标，如代谢率。当考虑到增加变温生物（如C）寿命的因素时，生理过程的测量尤为重要。因为降低外温动物代谢率的因素也往往会增加它们的寿命。本研究将利用RNAi技术对C.并将这些操作与对这些动物的代谢率测量结合联合收割机。 最终，这种分析最有趣的结果之一将是揭示是否有任何长寿的RNAi处理过的蠕虫也保持正常的代谢率。这种蠕虫可以识别影响代谢率"下游"过程的候选基因，并为衰老的原因和减缓衰老的机制提供有价值的见解。

Application in response to research objective 21 "Genetics, Behavior, Social Factors and Aging" of the NIA pilot research grant program. While the mechanisms that cause aging have recently become the subject of an intensive research effort, the multi-factorial nature of aging makes it difficult to disentangle the factors responsible for senescence. A powerful method towards identifying the causal mechanisms of aging is to study genetic mutations or manipulations that extend longevity using an intensively analyzed model organism, such as the nematode Caenorhabditis elegans. A new method for identifying genes affecting longevity in C. elegans is the use of RNA-mediated inference (RNAi). RNAi silences gene expression through the use of double-stranded RNA that target specific mRNAs for degradation. RNAi has proven itself to be a valuable tool to study aging in C. elegans and has been used to identify hundreds of genes that influence longevity in C. elegans. However, to provide true insight into the aging process, studies of C. elegans and aging must also assay other measures of physiological function such as metabolic rates, in addition to chronological life span. Measures of physiological processes are especially important when considering factors that increase longevity in an ectothermic (poikilothermic) organism such as C. elegans because factors that reduce the metabolic rate of ectotherms also tend to increase their longevity. This research will use RNAi to manipulate gene function in C. elegans and to combine these manipulations with metabolic rate measurements on these animals. Ultimately one of the most interesting outcomes of such an analysis will be to reveal whether any of the longlived RNAi treated worms also retain normal metabolic rates. Such worms could identify candidate genes affecting processes that act "downstream" from the metabolic rate and provide valuable insights into the causes of aging and mechanisms by which it can be attenuated.