Sleep-wake and circadian behavior in brain-specific sirtuin 1 knockout mice and effects of nicotinamide mononucleotide supplementation.

Sirtuin 1 (SIRT1) is implicated in sleep regulation, but there have been a limited number of sleep studies related to SIRT1. We aim to determine the impacts of the brain-specific loss of SIRT1 on sleep and circadian rhythm. We first characterized circadian periods and sleep phenotypes in baseline and recovery sleep in brain-specific Sirt1 knockout (BKO) and littermate wild-type (WT) mice. We found that there were no differences in sleep architecture, amount of each vigilance state, and sleep homeostasis between genotypes, suggesting that brain SIRT1 functionally plays minor roles in sleep-wake regulation. However, in accordance with prior work, loss of Sirt1 caused decreased delta power during non-REM sleep. In addition, there was no difference in intrinsic circadian periods between genotypes. We also provide the first preclinical evidence of whether nicotinamide mononucleotide (NMN) treatment directly improves sleep by administering it acutely (intraperitoneally for 10 days) and chronically (orally for 2 months). However, neither acute nor chronic treatment changed sleep duration and quality compared to the control session in middle-aged WT and BKO mice. Considering our findings and previous studies, the clinically reported improvement in muscle function and energy metabolism may indirectly contribute to the potential benefits of NMN on sleep quality and fatigue in the elderly.