Formal Analysis of the Impact of Feeding on Hepatocyte Circadian Oscillators

Abstract

Circadian rhythms are oscillations following daily periodic cycles and are respon sible for time keeping and timely activation and suppression of bodily functions. As such they are integrated in every aspect of the organism: its behaviour, health, and activities. As a result, they are sensitive enough to adapt but, at the same time, robust enough to not breakdown while functioning. A pipeline of computa tional and formal modelling techniques was enhanced with a novel application of network analysis to study a particular circadian system, the hepatocyte circadian oscillators. Study covered their behaviour and functioning with regards to the feeding regimens and feeding induced entrainment of the system. It was found that the circadian system was highly robust, and was always able to evolve even in the direst of circumstances. Based on this robustness, different feeding regimens were simulated to study the entrainment of the oscillators in response to changes in the regimens. The simulation results confirmed that among the different regimens modelled, the regimens consisting of 2–3 meals per day were consistent and pro duced healthy protein expressions and oscillations, which, based on other wet-lab studies, are linked with reduced ageing, improved health and better longevity.