One study concluded that women who work in shifts are less susceptible than men to the risk of suffering from metabolic disorders induced by disruption of the circadian cycle caused by changes in working hours. Its authors suggest that this female resistance to circadian misalignment may historically be linked to a biological need to bear children.
Observational study on 90,000 UK workers has been completed by searching in mice for the mechanisms underlying the adverse health effects of shift work. Thus, among other results, it has been observed that male rats exposed to circadian stress have biological changes in the liver and intestinal microbiome that do not appear in females. Among other findings, the article addresses a novel point of view to explain gender differences in resistance to circadian misalignment and the possibility of sexual dimorphism (anatomical differences between males and females of the same species).
The new data, published today in the journal Science Transnational Medicine, comes from work done by various departments at the University of Pennsylvania (Philadelphia), led by Sean Anderson, a researcher at the Institute for Translational and Therapeutic Medicine and a professor emeritus at the University of Pennsylvania. Perelman College of Medicine. The authors believe that these findings “may have societal implications affecting the future redesign of shift work, including attitudes to transmeridian travel.”
These are the dangers of less and poor sleep
These are the dangers of less and poor sleep
It is known that the circadian rhythm, best known as the internal body clock that regulates sleep schedules, also regulates metabolic processes such as insulin sensitivity and lipid metabolism. It has also been observed that night shift workers, especially men, as well as other people with disrupted circadian rhythms, are at a higher risk of metabolic diseases such as diabetes. To find out why this happens, the researchers analyzed records from 51,990 women and 40,335 men with a history of shift work in the United Kingdom Biobank, first verifying that both sexes compared workers at certain hours. presented with an increased risk of metabolic syndrome.
The researchers then compared the microbiome, metabolic profiles and behavioral patterns of male and female mice that had been fed high-fat diets, finding that females exposed to abnormal day-night cycles were not overly affected. However, they did record changes in the men’s gut microbiome, liver metabolism and blood pressure, differences that disappeared when the scientists suppressed the gut microbiome of both groups with antibiotic treatment.
Disadvantages of Circadian Misalignment
So far, various longitudinal studies have been linking shift work with cardiometabolic disorders, but without elucidating the causes or mechanisms of the disease. This research group has developed a mouse model based on this type of alternating schedule to study circadian misalignment in both sexes, a phenomenon that occurs when eating and sleeping oppose the natural orientations of the light/dark cycle. It happens. This internal imbalance is manifested in various metabolic diseases due to alterations of homeostasis.
Behavioral and transcriptional rhythmicity was preserved in female mice despite exposure to the misalignment. Women were protected from the cardiometabolic effects seen in men, even on a high-fat diet. Only male mice had tissue-level changes with dysbiosis of the gut microbiome.
Women in the UK Biobank showed a stronger circadian rhythm and a lower incidence of metabolic syndrome than men. “We have shown that female mice are more resistant to chronic circadian misalignment than males and that these differences are conserved in humans,” Anderson said.
The authors point out that circadian rhythms are endogenous oscillations that underlie nearly every aspect of our physiology, from gene transcription to behavior. These rhythms are directed by the suprachiasmatic nucleus in the hypothalamus and organized through a hierarchical network of molecular clocks. They are known to compartmentalize many homeostatic functions, such as our sleep-wake cycles, so that they occur during optimal times of day, but their continued disruption can lead to poor health.
Endogenous oscillations are also evident in more subtle functions, such as insulin sensitivity, lipid metabolism, and renal filtration. There are even genetic and environmental predispositions that are associated with a noticeable loss of circadian rhythms, which can lead to poor health. However it does not precisely understand which mechanisms trigger the risks.
Other studies show that genetic disruption of the molecular clock results in more severe cardiometabolic dysfunction in male mice than in female mice, and that male mice also gain significantly more weight after 12 weeks of biweekly phasing than female mice. happens, whether they are phased or not. ovariectomy or estrogen replacement.
Some recent meta-analyses pooled data on an increased risk of developing hypertension in men working shifts, and it is also associated with the development of diabetes and metabolic syndrome over women working similar shifts. However, another meta-analysis provided conflicting data, with a greater participation of women in shift work.
Safety Beyond Estrogen
The most important results can be summarized that after circadian rhythm disturbance, female mice achieved resynchronization faster than males; that chronic circadian misalignment abrogates transcriptomic rhythms only in male mice, and that it alters the gut microbiome of male mice, but not female mice; The cardiometabolic effects of misalignment differed between sexes and ovariectomized rats maintained oscillations in the central circadian clock machinery even after misalignment.
The authors emphasize that they observed sexual dimorphism indicating that there are other factors beyond estrogen signaling in adulthood. Other studies had previously shown that estrogen affects the circadian response to light, and mice that had their ovaries removed showed an intermediate phenotypic response compared to male mice following circadian cycle misalignment.
This intermediate phenotype indicates that, while important, estrogen signaling in adulthood is not the only factor conferring protection against misalignment in female mice. “One caveat to this approach is that ovariectomy completely abolishes whole-body estrogen signaling, confounding estrogen’s role in circadian rhythms with its known protective effect in cardiometabolic disease,” says Anderson.
On the other hand, circadian rhythm disturbance was associated with a spectrum of disease and aging phenotypes, suggesting that a stronger circadian rhythm in women may be relevant beyond the context of shift work and misalignment. “These analyzes integrate data across multiple domains and on the sexually dimorphic effects of circadian misalignment in both mice and humans,” the authors stress, acknowledging the study’s limitations such as the detection of transcriptional oscillations or feeding rhythms at the individual level of mice. do not apply; Or in the human study, they did not investigate whether the type of shift (rotating, standing etc…) affected the risk of cardiometabolic disease.
“However, we have shown that there is substantial sexual dimorphism not only in basal circadian rhythms, but also in response to chronic circadian misalignment. We previously suggested that sleep disruption and resilience to circadian misalignment may arise from a biological need to which reflects the historically prominent role women have played in raising children.
That sexual dimorphism. Covering everything the researchers measured – from behavior and phenotype to the transcriptome, proteome and microbiome – it was also conserved in human participants from the UK Biobank. “Although these results highlight conserved between-sex differences in circadian rhythms, they illustrate the apparent resistance of women to the adverse consequences of circadian misalignment,” the authors conclude, adding that these findings “may have societal implications.” is.”, From” Design of shift work schedules for the possibilities of handling transmeridian flights”.