The mammalian circadian clock is located in the suprachiasmatic nucleus (SCN) and consists of a network of coupled neurons, which are entrained to the environmental light-dark cycle. The phase... Show moreThe mammalian circadian clock is located in the suprachiasmatic nucleus (SCN) and consists of a network of coupled neurons, which are entrained to the environmental light-dark cycle. The phase coherence of the neurons is plastic and driven by the duration of daylight. With aging, the capacity to behaviorally adapt to seasonal changes in photoperiod reduces. The mechanisms underlying photoperiodic adaptation are largely unknown, but are important to unravel for the development of novel interventions to improve the quality of life of the elderly. We analyzed the phase coherence of single-cell PERIOD2::LUCIFERASE (PER2::LUC) expression rhythms in the SCN of young and old mice entrained to either long or short photoperiod. The phase coherence was used as input to a 2-community noisy Kuramoto model to estimate the coupling strength between and within neuronal subpopulations. The model revealed a correlation between coupling strength and photoperiod-induced changes in the phase relationship among neurons, suggesting a functional link. We found that the SCN of young mice adapts in coupling strength over a large range, with weak coupling in long photoperiod (LP) and strong coupling in short photoperiod (SP). In aged mice, we also found weak coupling in LP, but a reduced capacity to reach strong coupling in SP. The inability to respond with an increase in coupling strength suggests that manipulation of photoperiod is not a suitable strategy to enhance clock function with aging. We conclude that the inability of aged mice to reach strong coupling contributes to deficits in behavioral adaptation to seasonal changes in photoperiod. Show less
Aging impairs circadian clock function, leading to disrupted sleep-wake patterns and a reduced capability to adapt to changes in environmental light conditions. This makes shift work or the... Show moreAging impairs circadian clock function, leading to disrupted sleep-wake patterns and a reduced capability to adapt to changes in environmental light conditions. This makes shift work or the changing of time zones challenging for the elderly and, importantly, is associated with the development of age-related diseases. However, it is unclear what levels of the clock machinery are affected by aging, which is relevant for the development of targeted interventions. We found that naturally aged mice of >24 months had a reduced rhythm amplitude in behavior compared with young controls (3-6 months). Moreover, the old animals had a strongly reduced ability to adapt to short photoperiods. Recording PER2::LUC protein expression in the suprachiasmatic nucleus revealed no impairment of the rhythms in PER2 protein under the 3 different photoperiods tested (LD: 8:16, 12:12, and 16:8). Thus, we observed a discrepancy between the behavioral phenotype and the molecular clock, and we conclude that the aging-related deficits emerge downstream of the core molecular clock. Since it is known that aging affects several intracellular and membrane components of the central clock cells, it is likely that an impairment of the interaction between the molecular clock and these components is contributing to the deficits in photoperiod adaptation. Show less
Aguilar-Roblero, R.; Quinto, D.; Baez-Ruiz, A.; Chavez, J.L.; Belin, A.C.; Diaz-Munoz, M.; ... ; Lundkvist, G. 2016
