Chronodisruption is a concept in the field of circadian biology that refers to the disturbance or alteration of the body's natural biological rhythms, for example the sleep-wake cycle, due to various environmental factors. The human body is synchronized to a 24-hour light-dark cycle, which is essential for maintaining optimal health and well-being. However, modern lifestyles —which involve exposure to artificial light (especially during nighttime), irregular sleep schedules, and shift work — can disrupt this natural rhythm, leading to a range of adverse physiological outcomes. Chronodisruption has been linked to a variety of health disorders and diseases, including neurodegenerative diseases, diabetes, mood disorders, cardiovascular disease, and cancer. Such disruptors can lead to dysregulation of hormones and neurotransmitters, though researchers continue to investigate the physiological implications of chronodisruption. Indeed, research in chronobiology is rapidly advancing, with an increasing focus on understanding the underlying mechanisms of chronodisruption and developing strategies to prevent or mitigate its adverse effects. This includes the development of pharmacological interventions, as well as lifestyle modifications such as optimizing one's sleeping environment and timing of meals and physical activity.
Chronodisruption and cancer People with chronodisruption have increased risk for certain types of cancer. Chronodisruption is demonstrated to have a causal role in cancer cell growth and tumor progression in rodents. In 2020, the International Agency for Research on Cancer (IARC) found that chronodisruption due to chronic night-shift work is a probable carcinogen (cancer-causing agent) in humans.
In humans Chronodisruption, in the form of shift work, increases the risk of breast cancer in women by about 50%. The risk of developing other forms of cancers, such as prostate cancer in men and colorectal cancer in women, may also increase with chronodisruption; studies in this area have shown modest, but statistically significant, associations. Chronodisruption is associated with impeded homeostasis of the cell cycle; this is correlated with malignant growth acceleration and cancer, potentially due to obstruction of normal DNA damage repair.
In model organisms In the studies investigating the relationship between experimental chronic jet lag and tumor progression done by Filipski et al., mice were kept under either 12:12 Light-Dark cycles (LD cycles) or under 12:12 LD cycles that would phase-advance by eight hours every two days. Upon injection with Glasgow osteosarcoma cells, a rapid acceleration in cancer cell proliferation rate was observed in the mice experiencing an 8-hour phase advance every two days compared to the mice not experiencing phase advance. Moreover, clock gene expressions (e.g. mPer2) were suppressed in mice subjected to repeated phase advance, while the daily rhythm in clock gene expression was maintained in mice in a typical 12:12 LD cycle. The down-regulation of the p53 gene and over-expression of the c-Myc gene associated with the clock disturbance may also have contributed to tumor progression. Melatonin is known to be an endogenously produced oncostatic agent that inhibits tumor cell growth via various potential mechanisms. Studies showed that perfusing the human breast cancer xenografts growing in animals in melatonin-rich blood collected from premenopausal women significantly inhibited all signs of rapid cancer cell proliferation. On the other hand, melatonin-deficient blood collected from the same set of women failed to restrict tumor growth. In the originals studies done by Filipski et al., a mouse strain named B6D2F1, which had a low level of circulating melatonin, was used. Although no definite conclusion can be made on the possible effects of melatonin on cancer development in B6D2F1 mice based on the original studies, a general statement can be made: besides the direct effects of internal desynchronization with the external environment, the accelerated rate of cancer cell proliferation may also be a consequence of relative melatonin deficiency caused by chronodisruption. Extreme cases of chronic jet lag (6-hour advances every week last equal to or more than 4 weeks under experimental setting) were observed to cause premature death in aged male mice compared to their counterparts kept in stable external LD cycles. This consequence was not observed in mice experiencing chronic phase delays. This showed that persistent internal desynchronization as a result of repeated phase advances may be associated with reduced longevity. The findings may have great implications for shift workers and people that frequently experience transmeridian travels that advance their internal clock. Recent studies since 2016 in mice have shown that chronic jet-lag models accelerates tumorigenesis in genetic models of lung cancer, liver cancer, colorectal cancer, and skin cancer. It has been suggested that chronodisruption is an "Hallmark of Systemic Disease".
Chronodisruption and cardiovascular disease Chronodisruption is correlated with an increased risk for cardiovascular disease in humans. Experiments involving light-dark cycle manipulations, internal period mutations, and clock gene disruptions in rodents provide insights into the relationship between chronodisruption and the risk of cardiovascular diseases.
In humans Chronodisruption is associated with a significantly increased risk of cardiovascular disease in humans. Shift work has been implicated as a major risk factor for coronary heart disease, hypertension, ischemic stroke, and sudden cardiac death. Social jet lag, discrepancy between the schedule of working days and free days or misalignment between biological time and social time, may also be associated with increases in cardiovascular disease risk, as evidenced by increased triglyceride levels, decreased high-density lipoprotein-cholesterol levels, and decreased insulin sensitivity.
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