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Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fatty acids (PUFAs), which promotes starvation resistance and extends  Caenorhabditis elegans  life span. Upon fasting,  C. elegans  induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing  C. elegans  culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of  C. elegans  or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of  C. elegans  autophagy components reverses the increase in life span conferred by supplementing the  C. elegans  diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs.

ω-6 Polyunsaturated fatty acids extend life span through the activation of autophagy