Molecular circadian rhythms in humans: effects of age

Suprachiasmic nucleus (SCN) cells are not the only cells that possess the oscillatory machinery of the circadian rhythm. The same molecules are also present in peripheral tissues, such as the fibroblasts, which have a cell-autonomous and self-sustained circadian rhythm providing an excellent model to study the molecular and biochemical mechanisms of mammalian circadian systems in vitro. For human beings in general, circadian disturbances have been shown with age such as higher prevalence of early morning awakening and difficulties in maintaining sleep. Nevertheless, the origin of this phenomenon is unknown. In our study, we addressed the question of whether fibroblasts reflect age-related differences in the circadian period length in vitro, that parallel changes in subject circadian phase in vivo. For this purpose, we are currently investigating the period length of the skin fibroblasts from young and elderly subjects (young: ≤30 years old; elderly: ≥60 years old; sex-matched). In addition we collect data about the chronotype of the subjects by analysing the Munich Chronotype Questionnaire. Fibroblasts are isolated from skin biopsies collected from the buttock of the subjects and infected with an engineered lentiviral circadian reporter that permits the characterization of circadian rhythms in vitro. Measurements (3p. biopsy; n=6 total p. subject) are conducted over a time period of 5 days. Supported by EU Grant #LSHM-CT-2006–018741 and grant from Désireé&Niels Yde Found.