Circadian System and Ageing in Rodent Models

Circadian rhythms (CR), or the biological clock, are essential components of almost all living things and can be seen at cellular, behavioural, or physiological levels. In the previous chapters, we discussed how a rhythm is generated in synchrony to the external environment, how the clock operates, and what its regulating factors are. However, as animals age, their internal clocks become less regular and more susceptible to disrupting external stimuli. In this chapter, we will discuss the physiology of the rodent circadian system, rhythms and clock gene disturbance in aging and age-related disorders, and models of genetic (clock gene mutant/knockout mice) and environmental (light-dark regimes modification) circadian disturbance. As we’ve highlighted, the circadian timekeeping mechanism in mammals is extremely conserved both anatomically and genetically. It is set up hierarchically, with the central pacemaker able to relay information to the periphery oscillators to synchronize its rhythm with outside light cues. The components of the circadian clock at the cellular level are the clock genes’ protein products, which form a number of transcription-translation feedback loops. Internal cycles last roughly 24 h, but they are constantly altered by signals from the central pacemaker. The primary element in humoral timekeeping is thought to be melatonin. Circadian rhythmic functions include rest-activity cycles, hormone synthesis, and antioxidant activities. CR are altered as a result of the aging circadian system’s inability to accurately manage peripheral rhythms. In addition to sleep loss or fragmentation, age-related deterioration in circadian function can severely worsen life quality. The circadian clock also has a role in cognitive, cardiovascular, and metabolic problems; hence chronodisruption may significantly exacerbate these maladies. According to animal models, age-related illnesses and rapid aging are caused by CR disruption, which can occur due to environmental or hereditary factors. In mammalian organisms, nearly all physiological systems are subject to diurnal fluctuations. It must meet three criteria in order to be considered a “circadian rhythm”: (a) have an endogenous period of about 24 h; (b) be able to entrain in response to outside stimuli; and (c) display temperature adjustment. The production and secretion of practically all hormones, different metabolic processes, gene expression, body temperature, heart rate, and blood pressure are only a few examples of rhythmic functioning (Bell-Pedersen et al. 2005). Only a few of these, including locomotion, sleep-wake cycles, body temperature, and rhythms of eating and drinking, can, however, be assessed non-invasively (Nakamura et al. 2008). As a result, the majority of CR research focuses on these functions. Actograms, special plots where daily activity patterns are aligned with one another, are used to easily notice and evaluate the behavioural rhythm, which is the most obvious rhythm. Phase shifts may be visible with such a representation (Jud et al. 2005). Constant conditions (LL or DD), phase shift or jet lag, long or short light cycles, and total chronodisruption are among the techniques used to assess CR consolidation.