Abstract
In Caenorhabditis elegans, ablation of germline stem cells (GSCs) extends lifespan, but also increases fat accumulation and alters lipid metabolism, raising the intriguing question of how these effects might be related. Here, we show that a lack of GSCs results in a broad transcriptional reprogramming in which the conserved detoxification regulator SKN-1/Nrf increases stress resistance, proteasome activity, and longevity. SKN-1 also activates diverse lipid metabolism genes and reduces fat storage, thereby alleviating the increased fat accumulation caused by GSC absence. Surprisingly, SKN-1 is activated by signals from this fat, which appears to derive from unconsumed yolk that was produced for reproduction. We conclude that SKN-1 plays a direct role in maintaining lipid homeostasis in which it is activated by lipids. This SKN-1 function may explain the importance of mammalian Nrf proteins in fatty liver disease and suggest that particular endogenous or dietary lipids might promote health through SKN-1/Nrf.
Highlights
The nematode Caenorhabditis elegans has been invaluable for identifying mechanisms that slow aging and may prevent chronic disease (Kenyon, 2010)
The effects of germline stem cells (GSCs) loss in C. elegans provide a paradigm for investigating this problem, as well as interactions between a stem cell population and its environment
We determined that GSC inhibition leads to a broad transcriptional reprogramming in somatic tissues that involves activation of SKN-1, and that SKN-1 is required for many beneficial effects of GSC absence, including lifespan extension
Summary
The nematode Caenorhabditis elegans has been invaluable for identifying mechanisms that slow aging and may prevent chronic disease (Kenyon, 2010). GSC loss increases lifespan in Drosophila melanogaster (Flatt et al, 2008), and castration has been associated with longevity in men (Min et al, 2012), suggesting that this relationship might be conserved. These beneficial effects of GSC removal may have evolved to maximize reproductive fitness under adversity (Partridge et al, 2005; Kenyon, 2010).
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