Pandey Pritika, Wall P Kerr, Lopez Stephen R, Dubuisson Olga S, Zunica Elizabeth R M, Dantas Wagner S, Kirwan John P, Axelrod Christopher L, Johnson Alyssa E
Louisiana State University, Department of Biological Sciences, Baton Rouge, LA 70803.
Pennington Biomedical Research Center, Integrated Physiology and Molecular Medicine Laboratory, Baton Rouge, LA, 70808.
Res Sq. 2023 Jun 2:rs.3.rs-2882949. doi: 10.21203/rs.3.rs-2882949/v1.
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.
睡眠不足通常会对动物健康产生负面影响。然而，在基因（）中存在罕见基因突变的人类却是个例外；这些个体睡眠时间较少，但没有通常与睡眠剥夺相关的影响。因此，有人提出这种基因突变激活了补偿机制，使这些个体能够在较少睡眠的情况下茁壮成长。为了直接验证这一点，我们使用了一个模型来研究该基因突变对动物健康的影响。在果蝇睡眠神经元中表达人类基因足以模拟短睡眠表型，而且值得注意的是，突变体尽管睡眠时间减少，但健康状况改善且寿命显著延长。生理效应的改善部分是通过增强线粒体适应性和上调多种应激反应途径实现的。此外，我们提供的证据表明，促进健康途径的上调也有助于短睡眠表型，这种现象可能也适用于其他长寿模型。
