Sleep pressure triggers sleep fragmentation in aging - Celia Kjærby

Aging is associated with cognitive decline and fragmented sleep, but the mechanisms linking altered sleep microstructure to memory impairment remain unclear. Here, we show that elevated sleep pressure reveals a dysregulation of the locus coeruleus (LC)–norepinephrine (NE) system that disrupts NREM sleep organization in aged mice. Using 24-hour EEG/EMG recordings, we found that aged mice exhibit increased NREM sleep fragmentation and micro-arousals specifically during the active dark phase, while sleep during the inactive light phase is preserved.

Simultaneous fiber photometry of cortical NE dynamics revealed hyperactive infraslow NE fluctuations during NREM sleep in aged mice under conditions of high sleep pressure, including prolonged wakefulness and sleep deprivation. These altered NE dynamics were associated with prolonged delta-rich, unconsolidated NREM sleep and reduced sigma-band spindle clustering. Consistent with these physiological changes, aged mice displayed impaired spatial memory performance that correlated with increased sleep fragmentation and reduced spindle organization.

Together, our findings identify sleep-pressure–dependent LC-NE hyperactivity as a key mechanism linking age-related sleep fragmentation to impaired memory consolidation.