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LiFE, a multimodal circadian intervention, improves sleep, glycemic control, and recognition memory
Yu Shi1, Stephen D Rozen1, Jordan T Swint1
1Department of Biology, University of Virginia; Charlottesville, Virginia 22904, USA.
Biorxiv : the Preprint Server for Biology
|March 27, 2026
Summary
This study introduces a lifestyle intervention (LiFE) combining light, food, and exercise to improve sleep and circadian rhythms. LiFE enhanced sleep, metabolic health, and memory in mice, showing potential for Alzheimer's disease treatment.
Area of Science:
- Neuroscience
- Chronobiology
- Metabolic Health
Background:
- Sleep and circadian rhythms are crucial for mammalian health.
- Disruptions in these systems are linked to metabolic disorders and neurodegenerative diseases like Alzheimer's disease (AD).
- Current treatments often focus on single interventions, potentially missing synergistic effects.
Purpose of the Study:
- To develop and evaluate a multimodal lifestyle intervention (LiFE) integrating light, feeding, and exercise cues.
- To assess LiFE's impact on circadian rhythmicity, sleep patterns, metabolic health, and cognitive function in mice.
- To explore LiFE's therapeutic potential in mouse models of Alzheimer's disease.
Main Methods:
- Developed a daily lifestyle intervention (LiFE) combining controlled light exposure, feeding schedules, and exercise.
- Administered LiFE to wild-type (WT) mice and two AD mouse models (5xFAD and 5xFAD/PS19).
- Monitored activity patterns, sleep duration, suprachiasmatic nucleus (SCN) rhythmicity, glucose metabolism, and cognitive performance (recognition memory, motor function).
Main Results:
- LiFE consolidated nocturnal activity, enhanced SCN rhythmicity, and increased sleep time in WT mice.
- LiFE improved glucose regulation, lowering baseline blood glucose and improving glucose tolerance without altering caloric intake.
- Long-term LiFE treatment enhanced recognition memory in WT mice and showed trends toward improved motor performance and recognition memory in AD models, with subtle reductions in AD pathology.
Conclusions:
- Multimodal circadian chronotherapy using LiFE effectively strengthens circadian rhythms and improves sleep and metabolic health.
- LiFE demonstrates potential as a non-pharmacological therapeutic strategy for cognitive and metabolic dysfunctions, including those associated with Alzheimer's disease.
- Integrated environmental cues offer a promising avenue for promoting overall health and mitigating disease progression.
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