Abstract
RNA interference (RNAi) provides an important tool for gene function discovery. It has been widely exploited in Caenorhabditis elegans ageing research because it does not appear to have any non-specific effects on ageing-related traits in that model organism. We show here that ubiquitous, adult-onset activation of the RNAi machinery, achieved by expressing a double stranded RNA targeting GFP or lacZ for degradation, or by increasing expression of Dicer substantially reduces lifespan in Drosophila melanogaster. Induction of GFPRNAi construct also alters the response of lifespan to nutrition, exacerbating the lifespan-shortening effects of food containing a high quantity of yeast. Our study indicates that activation of the RNAi machinery may have sequence-independent side-effects on lifespan, and that caution needs to be exercised when employing ubiquitous RNAi in Drosophila ageing studies. However, we also show that RNAi restricted to certain tissues may not be detrimental to lifespan.
Highlights
Ageing and the associated functional decline are a major medical and socioeconomic concern for developed countries [1,2]
Activation of the RNA interference (RNAi) machinery appears to decrease lifespan in Drosophila
We show here that ubiquitously driving a construct expressing double-stranded RNA (dsRNA) containing a portion of the GFP or LacZ protein-coding sequence, or ubiquitous induction of Dicer, has a negative effect on Drosophila lifespan
Summary
Ageing and the associated functional decline are a major medical and socioeconomic concern for developed countries [1,2]. Despite the complexity of the process, we known that ageing can be modulated by pharmacological, genetic and environmental interventions [2] This has resulted in an explosion in research activity aimed at identifying the genes, pathways and processes that can be used as potential targets for interventions into human ageing, to achieve better health for older people. These efforts have been successful in identifying numerous longevity determinants, especially in the simpler, genetically-amenable animal models such as the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. RNAi can be triggered by exogenously-provided dsRNA and for this reason it has been widely exploited for gene-function analysis [3]
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