A familial natural short sleep mutation promotes healthy aging and extends lifespan in .

Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the gene ( ) present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the mutation activates compensatory mechanisms that allows these individuals to thrive with less sleep. To test this directly, we used a model to study the effects of the mutation on animal health. Expression of human in fly sleep neurons was sufficient to mimic the short sleep phenotype and, remarkably, mutants lived significantly longer with improved health despite sleeping less. The improved physiological effects were enabled, in part, by enhanced mitochondrial fitness and upregulation of multiple stress response pathways. Moreover, we provide evidence that upregulation of pro-health pathways also contributes to the short sleep phenotype, and this phenomenon may extend to other pro-longevity models.