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Circadian clock resetting in the mouse changes with age

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Abstract

The most widely recognised consequence of normal age-related changes in biological timing is the sleep disruption that appears in old age and diminishes the quality of life. These sleep disorders are part of the normal ageing process and consist primarily of increased amounts of wakefulness and reduced amounts of deep sleep. Changes in the amplitude and timing of the sleep-wake cycle appear to represent, at least in part, a loss of effective circadian regulation of sleep. Understanding alterations in the characteristics of stimuli that help to consolidate internal rhythms will lead to recommendations to improve synchronisation in old age. Converging evidence from both human and animal studies indicate that senescence is associated with alterations in the neural structure thought to be primarily responsible for the generation of the circadian oscillation, the suprachiasmatic nuclei (SCN). Work has shown that there are changes in the anatomy, physiology and ability of the clock to reset in response to stimuli with age. Therefore it is possible that at least some of the observed age-related changes in sleep and circadian timing could be mediated at the level of the SCN. The SCN contain a circadian clock whose activity can be recorded in vitro for several days. We have tested the response of the circadian clock to a number of neurochemicals that reset the clock in a manner similar to light, including glutamate, N-methyl-D-aspartate (NMDA), gastrin-releasing peptide (GRP) and histamine (HA). In addition, we have also tested agents which phase shift in a pattern similar to behavioural ‘non-photic’ signals, including neuropeptide Y (NPY), serotonin (5HT) and gamma-aminobutyric acid (GABA). These were tested on the circadian clock in young and older mice (approximately 4 and 15 months old). We found deficits in the response to specific neurochemicals but not to others in our older mice. These results indicate that some changes seen in the responsiveness of the circadian clock to light with age may be mediated at the level of the SCN. Further, the responsiveness of the circadian clock with age is attenuated to some, but not all stimuli. This suggests that not all clock stimuli loose their effectiveness with age, and that it may be possible to compensate for deficits in clock performance by enhancing the strength of those stimulus pathways which are intact.

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Acknowledgements

We are grateful to Research into Ageing (UK) and the Wellcome Trust (UK) for financial support.

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  1. Department of Psychology, University of Glasgow, Glasgow, G12 8QB, Scotland

    Stephany M. Biello

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Biello, S.M. Circadian clock resetting in the mouse changes with age. AGE 31, 293–303 (2009). https://doi.org/10.1007/s11357-009-9102-7

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