Sleep disruption with aging in senescence-accelerated mice-prone 8 (SAMP8) mice and analysis of factors associated with age-related sleep fragmentation using RNA sequencing of the hypothalamus.

Aging is a risk factor for various disorders, and age-dependent changes in sleep parameters are involved in the pathogenesis of many diseases. Senescence-accelerated mice-prone 8 (SAMP8) have a short lifespan and show a disrupted circadian rhythm. However, little is known about how sleep parameters change with age in SAMP8. In this study, we evaluated changes in sleep parameters with aging in SAMP8 compared with those in senescence-accelerated mouse resistant 1 (SAMR1) as the control. Sleep quantity and fragmentation of sleep were evaluated at 4, 36, and 56 weeks of age using a PiezoSleep® system. The average duration of sleep episodes, reflected as the sleep fragmentation, decreased in an age-dependent manner in both SAMR1 and SAMP8, especially under light phase conditions. Interestingly, while the difference between SAMR1 and SAMP8 was not evident at 4 weeks of age, it was significantly reduced in SAMP8 at 36 and 56 weeks of age. These results suggest that the reduction of average sleep episode duration associated with the aging process was accelerated in SAMP8. To explore the mechanisms underlying the accelerated sleep fragmentation in SAMP8, we performed RNA sequencing on hypothalamic specimens obtained from SAMR1 and SAMP8 at 49 weeks of age, which revealed upregulation of type I interferon (IFN)-responsive genes in the SAMP8 hypothalamus. Furthermore, serum IFN-α levels at 49 weeks of age were higher in SAMP8 compared with those in SAMR1, suggesting that elevated IFN-α production in SAMP8 could be associated with the sleep fragmentation.