Many heart attacks occur in the early morning hours. But not only heart problems: many other diseases usually appear early in the morning. Now, an investigation into Weizmann Institute of Sciences (Israel), has discovered a possible explanation for this mysterious phenomenon.
In a study published in ‘Cellular metabolism‘, scientists have discovered that a key component of our circadian clock (the internal 24-hour molecular clock that operates in every cell) also regulates the body’s response to oxygen deficiency. This component, which undergoes changes during the day and night, could influence the timing of outbreaks which are affected by the oxygen cycle in the body.
Him 2019 Nobel Prize in Physiology or Medicine was awarded to three researchers who discovered hypoxia-inducible factor 1-alpha (HIF-1α), the key protein that determines how each cell responds to a lack of oxygen.
As long as there is enough oxygen, the protein remains unstable and decomposes rapidly; but when there is a lack of oxygen, it stabilizes, accumulates and enters the nucleus of cells where it activates numerous vital genes to respond to the lack of oxygen.
The study found that the BMAL1 protein, a key component of our circadian clock, also plays an important role in the body’s response to oxygen deficiency and is required to stabilize and activate the HIF-1α protein.
Furthermore, it suggests that BMAL1 is more than just a “booster” and that it plays an HIF-1α-independent role in activating the body’s plan to cope with oxygen deprivation. These new findings may explain why the body’s response to oxygen deficiency and ability to deal with various medical conditions changes throughout the day and night.
Protein by day, protein by night
The work demonstrated that HIF-1α and BMAL1 proteins are critical for activating the necessary genetic mechanisms against hypoxia. Using genetically modified mice that were missing one or both proteins in the liver, the researchers found that HIF-1α did not accumulate without BMAL1, affecting the response to hypoxia. Furthermore, mice lacking both proteins had high mortality in hypoxia during the nightassociated with circadian variations in BMAL1.
Surprisingly, although the mice had mild liver damage, the cause of death was related to the lung’s low ability to absorb oxygen, a phenomenon similar to hepatopulmonary syndrome in humans. This animal model could help study the mechanisms of this condition and develop new therapies.
«We have identified an increase in the production of nitric oxide in the lungs, which causes the dilation of blood vessels. As a result, blood flows through the lungs much more quickly and does not deliver oxygen efficiently,” the authors write.
However, they acknowledge that they do not yet know by what mechanisms liver damage affects lung function, but initial results from our genetic mouse model point to an interesting group of proteins that may be part of the communication between the liver and lungs.
«In mice that developed hepatopulmonary syndrome, this communication was impaired. If you are proteins are also produced in humans and are truly related to the syndrome, they could serve as a target for future therapy,” they conclude.
How can individuals adjust their daily routines to align better with their circadian biology for improved health?
Interview Between Time.news Editor and Dr. Rachel Levin, Expert on Circadian Biology
Editor: Welcome, Dr. Levin! Thank you for joining us today. Your recent work at the Weizmann Institute of Sciences has shed light on a fascinating intersection between our internal clocks and health. To start off, can you explain the significance of the circadian clock and how it relates to health issues like heart attacks?
Dr. Levin: Thank you for having me! The circadian clock is our internal 24-hour molecular rhythm that regulates various physiological processes in our bodies, from hormone release to sleep-wake cycles. Interestingly, many heart attacks and other medical issues tend to peak in the early morning hours. Our recent study indicates that this timing might be influenced by how our bodies respond to oxygen deficiency, which is regulated by circadian proteins.
Editor: That’s intriguing! You mentioned the BMAL1 protein and its role in oxygen response. Could you elaborate on how BMAL1 interacts with the hypoxia-inducible factor 1-alpha, or HIF-1α?
Dr. Levin: Absolutely! HIF-1α is a crucial protein that helps cells respond to low oxygen levels. Normally, when there’s enough oxygen, HIF-1α is unstable and breaks down rapidly. However, under oxygen deprivation, it stabilizes and activates genes to help cells adapt. Our research found that BMAL1 is not just a booster for HIF-1α; it significantly enhances the body’s ability to respond to oxygen deficiency independently of HIF-1α. This means that BMAL1 plays a dual role in regulating how our body copes with oxygen levels throughout the day.
Editor: Fascinating! So, it seems that the body’s response to oxygen deprivation is not a static process but varies throughout the day. How might this discovery impact our understanding of treating diseases associated with oxygen deficiency?
Dr. Levin: Exactly! Knowing that the body’s ability to handle oxygen deprivation varies can lead to more personalized treatment approaches. For instance, therapies could be more effective if they’re timed with the body’s natural rhythms. Additionally, this research can help identify individuals at higher risk for certain conditions based on their circadian profiles, potentially improving preventative strategies in cardiology and other fields.
Editor: That sounds promising! How might this research be applied in a practical sense for everyday health? Should people consider their daily routines in light of this new information?
Dr. Levin: Yes, absolutely! Simple lifestyle adjustments, like maintaining regular sleep patterns and being mindful of when we engage in physically demanding activities, can play a crucial part in optimizing our health. For instance, people who have a history of cardiovascular issues might benefit from avoiding strenuous exercise in the early morning when risks are naturally elevated.
Editor: That’s valuable advice! What’s next for you and your team in this research area? Are there any upcoming studies or trials we should be on the lookout for?
Dr. Levin: We’re currently exploring how different environmental factors, such as light exposure and food intake timing, influence our circadian rhythms and subsequent health outcomes. We hope to broaden our understanding of the interplay between our biological clocks and various diseases through extensive studies and potentially trials that may help translate our findings into clinical practise.
Editor: We look forward to those developments! Dr. Levin, thank you for sharing your insights with us today. It’s clear that our understanding of health and disease is intricately linked to the rhythms of our bodies.
Dr. Levin: Thank you for having me! It’s an exciting time in circadian biology, and I appreciate the opportunity to discuss our findings.