Health risks associated with genetic alterations in internal clock system by external factors

Abstract

The circadian system maintains the main aspects of physiological and behavioral processes. Both circadian rhythm and sleep impact an organism's health through interaction with environmental factors. Variations in external factors influence the functionality of clock genes and disrupt 24-hour rhythmic cycle. The disrupted circadian rhythm and disregulated sleep affect an organism's health, thereby causing several disorders including cancer, depression and cardiac disorders. Considering the role of clock genes and environmental factors, extensive investigation is required focusing on pathways involved in development of life-threatening disorders. This review identifies the major risks and associated factors related with disruption in circadian system and sleep.

Influence of mental stress and environmental toxins on circadian clocks: Implications for redox regulation of the heart and cardioprotection

“…Lifestyle plays a huge role in disrupting circadian rhythms and therefore predisposing individuals to developing cardiovascular diseases. Desynchronization of the circadian rhythm can occur if individuals have irregular sleeping patterns or have a jet setting lifestyle with frequent flying, constantly working in changing shift patterns and being exposed to different light–dark environments, which leads to an increased risk of developing neurological disorders and cardiovascular disease (Khan et al, 2018). Per1 and Per2 shift faster compared to Clock when an individual is phase shifting and causes disruption of the circadian clock (Khan et al, 2018).…”

“…Desynchronization of the circadian rhythm can occur if individuals have irregular sleeping patterns or have a jet setting lifestyle with frequent flying, constantly working in changing shift patterns and being exposed to different light–dark environments, which leads to an increased risk of developing neurological disorders and cardiovascular disease (Khan et al, 2018). Per1 and Per2 shift faster compared to Clock when an individual is phase shifting and causes disruption of the circadian clock (Khan et al, 2018). Mutations in genes such as Bmal1 , Cry1 , Cry2 , Rora , and Clock can alter sleep patterns (Ko & Takahashi, 2006).…”

“…With industrialisation and globalisation, the importance of new environmental risk factors such as air pollution (Lelieveld et al, 2019; is becoming increasingly significant. In particular, traffic noise (from road, aircraft and railway) is a potential novel cardiovascular risk factor (Kempen, Casas, Pershagen, & Foraster, 2018) and a large body of evidence indicates that noise can cause cardiovascular, metabolic and mental disease, including hypertension, heart failure, myocardial infarction (MI), diabetes, arrhythmia, stroke, depression and anxiety disorders, observations that are mainly based on not only association studies but also controlled interventional studies . Robust epidemiological evidence for detrimental health effects of environmental risk factors and mechanistic insights into the underlying pathophysiology are mostly based on association studies (with only few controlled interventional studies) and exist for the environmental risk factors mental stress (e.g.…”

Aging and the clock: Perspective from flies to humans

“…As circadian disruption and desynchronization exacerbate numerous health conditions from metabolic diseases, cancers to neuropsychiatric disorders (Albrecht, ; Arble, Ramsey, Bass & Turek, ; Evans & Davidson, ; Golombek et al., ; James et al., ; Khan et al., , ; Scheer et al., ), it is important to understand the interactions and impacts that circadian dysfunction or desynchronization has on the aging process. Research in hamsters has shown that circadian disorganization resulting from a mismatch between the light‐dark cycle and the free‐running period results in severe cardiac pathologies and kidney disease (Martino et al., ).…”

Extracellular Acidosis Promotes Metastatic Potency via Decrease of the BMAL1 Circadian Clock Gene in Breast Cancer

“…The circadian clock maintains daily oscillation rhythms with a 24 h periodicity in all living organisms. It responds to stimuli from external environments such as light, which affect pathological and physiological functions [7]. Several genes are associated with the circadian clock, including brain and muscle Arnt-like protein-1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), period (PERs; Per1, Per2, and Per3), and cryptochromes (CRYs; Cry1 and Cry2), which form a complex network of transcription-translation feedback loops, post-translational modifications, and degradation [8,9].…”