Sleep disturbances, caused by jet lag, have probably been experienced by all transatlantic travelers. Jet lag reflects the limited phase-shifting capacity of the suprachiasmatic nucleus.125 Sudden 1-hour phase delays and advances, such as the ones caused by switching from summer time to winter time and vice versa, should not disrupt the circadian cycle, Inhibitors,research,lifescience,medical since these phase changes are well within the synchronization capacity of the clock. However, several days are required to adapt the circadian pacemaker to abrupt and large CDK activity daytime changes caused by transatlantic flights. Jet lag not only affects sleep-wake cycles, but also peripheral organs, such as the gastrointestinal

tract, liver, pancréas, and the kidney.126 As a consequence, heavy meals absorbed at “inadequate” daytimes after a transatlantic flight may cause indigestion. Moreover, during the jet lag period “poorly timed” urine production by the kidney may increase the frequency of urination during night hours. Adaptation is achieved faster after westbound journeys Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical than after eastbound journeys, presumably since the SCN has a greater capacity for phase delays than phase advances.125 This was documented in a rather objective manner by examining

the performance of top-class German athletes after transatlantic flights to Atlanta (westbound) or Osaka (eastbound). Jet lag-associated drops in performance disappeared after 5 days in Atlanta, but only after 7 days in Osaka.127 While occasional episodes of jet lag have probably no consequences on morbidity, chronic jet lag suffered by nurses and flight attendants on rotation shift work during extended time periods has been reported to significantly

increase breast cancer Inhibitors,research,lifescience,medical risk.128 Moreover, mice subjected to light-dark regimens causing chronic jet lag show Inhibitors,research,lifescience,medical a sharp increase in morbidity and mortality.129 If animals kept under such conditions receive tumor grafts, the tumors proliferate more rapidly than in control mice.130 The molecular mechanisms linking circadian rhythms to tumor biology remain to be elucidated, but several observations hint towards the implication because of Per genes. Thus, a large fraction of mPerl mutant mice die of cancer, most frequently of spontaneous lymphomas.131, 132 Perhaps relevant to the increased breast cancer incidence in women with chronically disrupted circadian rhythms, Chen and coworkers reported that 56 out of 59 tumor samples from Taiwanese woman displayed strongly deregulated PER1, PER2, and PER3 gene expression.133 In these tumors, epigenetic silencing through DNA methylation, rather than mutations was responsible for the reduced levels of PER proteins. Perturbation of circadian clock function can also cause psychiatric ailments, SAD (seasonal affective disorder) being probably the most common among them.