In mammals, the suprachiasmatic nucleus (SCN) functions as a circadian clock that drives 24-h rhythms in both physiology and behavior. The SCN is a multicellular oscillator in which individual neurons function as cell-autonomous oscillators. The production of a coherent output rhythm is dependent upon mutual synchronization among single cells and requires both synaptic communication and gap junctions. Changes in phase-synchronization between individual cells have consequences on the amplitude of the SCN’s electrical activity rhythm, and these changes play a major role in the ability to adapt to seasonal changes. Both aging and sleep deprivation negatively affect the circadian amplitude of the SCN, whereas behavioral activity (i.e., exercise) has a positive effect on amplitude. Given that the amplitude of the SCN’s electrical activity rhythm is essential for achieving robust rhythmicity in physiology and behavior, the mechanisms that underlie neuronal synchronization warrant further study. A growing body of evidence suggests that the functional integrity of the SCN contributes to health, well-being, cognitive performance, and alertness; in contrast, deterioration of the 24-h rhythm is a risk factor for neurodegenerative disease, cancer, depression, and sleep disorders.

The circadian clock provides the temporal framework for rhythmic behavioral and metabolic functions. In the modern era of industrialization, work, and social pressures, clock function is jeopardized, and can result in adverse and chronic effects on health. Understanding circadian clock function, particularly individual variation in diurnal phase preference (chronotype), and the molecular mechanisms underlying such chronotypes may lead to interventions that could abrogate clock dysfunction and improve human (and animal) health and welfare. Our preliminary studies suggested that fruit-flies, like humans, can be classified as early rising “larks” or late rising “owls,” providing a convenient model system for these types of studies. We have identified strains of flies showing increased preference for morning emergence (Early or E) from the pupal case, or more pronounced preference for evening emergence (Late or L). We have sampled pupae the day before eclosion (fourth day after pupariation) at 4 h intervals in the E and L strains, and examined differences in gene expression by RNA-seq. We have identified differentially expressed transcripts between the E and L strains, which provide candidate genes for subsequent studies of Drosophila chronotypes and their human orthologs.

The increase of life expectancy and the decline of biological functions with advancing age are impending obstacles for our society. In general, age-related changes can be separated into two processes. Primary aging is based on programs governing gradual changes which are generally not harmful. On the other hand, secondary aging or senescence is more aleatory in nature and it is at this stage that the progressive impairment of metabolic, physiological, and neurological functions increases the risk of death. Exploiting genetic animal models, we obtain more and more information on the underlying regulatory networks. The aim of this review is to identify potential links between the output of the circadian oscillator and secondary aging. The reasons to suspect such links rely on the fact that the mouse models without functional circadian clocks sometimes exhibit reduced life expectancy. This may be due to their inability to properly control and synchronize energy expenditure, affecting, for example, the integrity of neurons in the brain. Hence, it is tempting to speculate that re-synchronization of metabolic and physiological functions by the circadian clock may slow down the aging process.