More on Germ Cells and Fatty Acid Metabolism

A very readable editorial on recent research into the connection between germ cells and longevity: " For reasons still unknown, a roundworm without its germ cells lives 60% longer than one with those cells intact. And you don't even need to actually remove them - mutations that impair their proliferation also extend life. ... The authors began their exploration by searching for nuclear receptors that were required for the life-extension effect, reasoning that one or more such receptors were likely to play a key role in controlling longevity pathways. Using RNAi in long-lived worms with a known germline proliferation mutation, they shut down hundreds of receptors, looking for those that would reverse the lifespan extension. They found only one, called nhr-80, which they showed acted specifically within the germline-mediated longevity pathway, and not any of the several other pathways known to extend lifespan. This result provided the first experimental evidence that lifespan extension through ablation of the germline can occur in the absence of insulin signaling, one of the best characterized pathways affecting lifespan. Mutation of nhr-80 to prevent expression of the gene prevented the longevity effect, while overexpression increased it, in both cases only when germline cells were absent. ... As a transcription factor, NHR-80 regulates gene expression. Its known targets include a group of enzymes involved in lipid metabolism called desaturases. Desaturases convert saturated fatty acids, such as stearic acid, into unsaturated fatty acids, such as oleic acid, a conversion that significantly alters the physical and biological properties of the fats made from them. The authors show that genes for several desaturases are highly expressed in long-lived germline mutants. ... While worms are not humans, we share many of the same cellular mechanisms, and it is possible the same life-extending effects of this germline-loss/fatty acid increase pathway will be found in us."



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