Brain-specific loss of the sirtuin 1 (SIRT1) gene has surprisingly little effect on sleep architecture or circadian rhythms in mice, according to a study published in Scientific Reports. The study also provides the first preclinical test of nicotinamide mononucleotide (NMN) as a direct sleep aid — and finds no benefit.
What they found
Researchers generated brain-specific Sirt1 knockout (BKO) mice and compared their sleep and circadian behavior with wild-type littermates. They also tested both acute (intraperitoneal, 10 days) and chronic (oral, 2 months) NMN supplementation in middle-aged mice.
Key results:
- Sleep architecture: There were no differences between BKO and wild-type mice in the amount of each vigilance state (wake, NREM, REM), sleep architecture, or sleep homeostasis. Brain SIRT1 appears to play a minor role in sleep-wake regulation.
- Delta power: Consistent with prior work, loss of Sirt1 did cause a decrease in delta power during NREM sleep — the EEG slow wave activity that reflects sleep depth and intensity.
- Circadian rhythms: Intrinsic circadian periods did not differ between genotypes.
- NMN supplementation: Neither acute nor chronic NMN treatment changed sleep duration or quality compared with control conditions in middle-aged mice. This contrasts with some human studies suggesting NMN may improve sleep quality — the authors propose that any clinical benefits of NMN on sleep are likely indirect, resulting from improvements in muscle function and energy metabolism rather than direct sleep regulation.
Why it matters
SIRT1 is a well-known regulator of metabolism and aging, and previous work had linked it to sleep regulation. The finding that brain-specific SIRT1 knockout leaves sleep architecture largely intact suggests that SIRT1’s role in sleep is either redundant, compensated for by other pathways, or mediated through peripheral rather than central mechanisms.
The NMN finding is particularly relevant given the popularity of nicotinamide mononucleotide and NAD+ precursor supplements, which are marketed for anti-aging and sometimes for sleep improvement. This study provides the first direct preclinical evidence that NMN does not improve sleep in a controlled setting — though the caveat that middle-aged mice may not model age-related sleep decline is important.
Limits
The study tested middle-aged mice (equivalent to roughly middle-aged humans), not aged mice where SIRT1 decline may be more consequential. The NMN dosing regimens may not match the pharmacokinetics of human supplementation. Mouse sleep and human sleep differ in important ways, and these findings may not translate directly.
Bottom line
Brain SIRT1 is dispensable for most aspects of sleep-wake regulation in mice. NMN supplementation, whether acute or chronic, does not improve sleep duration or quality in middle-aged mice, suggesting any clinical sleep benefits of NMN are indirect.
Source
“Sleep-wake and circadian behavior in brain-specific sirtuin 1 knockout mice and effects of nicotinamide mononucleotide supplementation.” Scientific Reports, June 23, 2026. DOI: 10.1038/s41598-026-XXXXX