Modeling and Analysis of the Impacts of Jet Lag on Circadian Clock and its role in Cancer

Abstract

Circadian rhythms maintain a 24 hour oscillation pattern in metabolic, physiological and behavioral processes in all living organisms. Circadian rhythms are organized as biochemical networks located in hypothalamus and peripheral tissues. Rhythmicity in the expression of circadian clock genes plays a vital role in regulating the process of cell division and DNA damage control. The oncogenic protein, MYC and the tumor suppressor, p53 are directly influenced by the circadian clock. Jet lag and altered sleep/wake schedules prominently affect the expression of molecular clock genes. This study is focused on developing a Petri Net model to analyze the impacts of long term jet lag on the circadian clock and its probable role in tumor progression. The results depict that jet lag disrupts the normal rhythmic behavior and expression of the circadian clock proteins. This dis ruption leads to persistent expression of MYC and suppressed expression of p53. Thus, it can be inferred that jet lag altered circadian clock negatively affects the expression of cell cycle regulatory genes causing uncontrolled proliferation of tumor cells.