[
International Worm Meeting,
2015]
Many tissue-specific interventions have been shown to effect organismal aging in a cell non-autonomous manner. How aging is coordinated between multiple cells and tissues is still poorly understood. The intestine not only acts as site of food digestion and energy storage, but is also a major endocrine tissue in the worm. Several studies have indicated that the intestine is important for the regulation of systemic aging and key aging pathways are known to act either in the intestine or signal towards it.We identified a transporter protein that displays homology to a large family of evolutionarily conserved solute carriers (SLCs). SLCs have been shown to transport a wide variety of substances such as nutrients, hormones and drugs across cell membranes. Interestingly, we found that the cellular context is important in the regulation of aging: Intestine-specific knock-down of this transporter is sufficient to extend the lifespan of C. elegans, while RNAi in a wild-type background has no effect on longevity. We show that this transporter modulates the activity of several genes involved in fat metabolism and knock-down via RNAi reduces fat accumulation. We further show that the lifespan extending effect is independent of the FOXO transcription factor DAF-16. Surprisingly, we found that this transporter is required for the long-life of germline-less animals and knock-down of this gene prevents the activation of several key transcription factors. However, the activity of this transporter is not generally required for long life, since knocking down this gene does not shorten the long life of other longevity mutants.Current and future analysis will focus on the genetic requirements and aim to decipher the molecular mechanism of the different lifespan modulating effects of this transporter. In addition metabolomics analysis will aid to identify potential target molecules and help to widen our understanding of the role of metabolism in aging. More generally, these results demonstrate the importance of the cellular context for the physiological function of factors involved in the regulation of aging. .