Pandey, P., Wall, P.K., Lopez, S.R., Zunica, E.R.M., Dubuisson, O.S., Dantas, W.S., Davuluri, G., Taylor, A.L., Wall, T.K., Juge, H.J., Kirwan, J.P., Axelrod, C.L., Johnson, A.E. (2025). A familial natural short sleep mutation in dec2 extends healthspan and lifespan in Drosophila.  iScience 28(9): 113388.

FBrf0263488

Research paper

Sleep loss typically imposes negative effects on animal health. However, humans with rare genetic mutations in the dec2 gene present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the dec2 short sleep mutations activate compensatory mechanisms that allow these individuals to thrive with less sleep. To test this directly, we used a Drosophila model to study the effects of the dec2 [P384R] mutation on animal health. Expression of a human dec2 [P384R] mutation in sleep-controlling neurons reduces sleep, and, remarkably, the short sleeping flies live significantly longer with improved health. The improved physiological effects were enabled, in part, by enhanced mitochondrial fitness and upregulation of multiple stress response pathways. Additionally, we demonstrate that dec2 [P384R] boosts mitochondrial respiratory capacity in both flies and mammalian cells, suggesting a conserved mechanism by which this mutation promotes healthy aging.

PMC12450728 (PMC) (EuropePMC)