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Caffeine has been reported to delay aging and protect aging-associated disorders in  Caenorhabditis elegans . However, the effects of low concentration of caffeine and its analogs on lifespan are currently missing. Herein, we report that at much lower concentrations (as low as 10 μg/ml), caffeine extended the lifespan of  C. elegans  without affecting food intake and reproduction. The effect of caffeine was dependent on IGF-1-like pathway, although the insulin receptor homolog,  daf-2  allele,  e1371 , was dispensable. Four caffeine analogs, 1-methylxanthine, 7-methylxanthine, 1,3-dimethylxanthine, and 1,7-dimethylxanthine, also extended lifespan, whereas 3-methylxanthine and 3,7-dimethylxanthine did not exhibit lifespan-extending activity.

Low Concentrations of Caffeine and Its Analogs Extend the Lifespan of Caenorhabditis elegans by Modulating IGF-1-Like Pathway