Cancer Prevention: A Circadian Controlled Game
Why circadian biology matters most for cancer prevention
Just yesterday, I came across this tweet from Ken Berry.
Whenever somebody mentions skin cancer, my ears perk up since my work revolves around circadian biology, with skin cancer being an extension to that. I’ve studied quite a bit of the research on melanoma and non-melanoma skin cancer.
So is Ken Berry correct?
Not even close.
We can find a more accurate understanding when we study circadian biology.
What matters more for the prevention of cancer, circadian biology or food?
I’ll begin by saying that every pillar of health must be in order to PREVENT cancer. Light environment, nutrition, detoxification, exercise, all of it is a key part of the discussion. You should strive to have a well-rounded lifestyle.
I’m not saying you can eat like shit and get away with it.
I’m speaking on cancer prevention, not treatment when a cancer diagnosis is present.
Our first question is as follows:
What processes in the body are designed to protect us from cancer?
There are many of them
DNA repair mechanisms
Apoptosis
Autophagy
Cell cycle checkpoints
Tumor suppressor genes
Immune surveillance
Antioxidant defense systems
Epigenetic regulation
Hormonal regulation
Detoxification systems
Cellular senescence
Acute inflammatory response
Endogenous melatonin production
Angiogenesis inhibition
Metabolic regulation
Mitochondrial function
Proteostasis
Gut microbiota regulation
Hormone receptor sensitivity
Stem cell maintenance
Detoxification of xenobiotics
Epigenetic remodeling
Autocrine & Paracrine signaling
There are likely more, but I want you to understand one thing here:
Every single one of these processes is fundamentally under circadian control.
There is no doubt about this.
We’ll go through a good number of them below.
DNA Repair Mechanisms
The efficiency of DNA repair mechanisms, such as nucleotide excision repair (NER) and base excision repair (BER), fluctuates over the course of the day.
Circadian genes like CLOCK and BMAL1 regulate the expression of key DNA repair proteins, ensuring that DNA repair is most effective when the body is exposed to higher levels of DNA-damaging factors.
This is why you want to get any screening which involves radiation, like an X-ray, done in the late morning to early afternoon (~ 10 AM - 2 PM). This period is when the circadian-controlled DNA repair mechanisms are generally more active.
Do you think it’s a coincidence that this is also the timeframe when UV light from the sun manifests and is most intense? Of course not.
Apoptosis
Apoptosis is tightly regulated by the circadian clock.
Proteins that control the apoptotic pathway, including p53 and BAX, are influenced by circadian rhythms, with their activity peaking at specific times of the day. This timing helps the body remove damaged or abnormal cells more efficiently when necessary.
Is it any coincidence that Vitamin D3 from midday sunbathing + endogenous sub-cellular and circulatory melatonin from the light/dark cycle alignment are pro-apoptosis?
Autophagy
Autophagic activity follows a circadian pattern, with higher levels typically occurring during the night or fasting periods.
Circadian regulation of autophagy-related genes ensures that cellular cleanup and recycling processes are synchronized with the body’s metabolic needs and repair activities.
What’s pro-autophagy?
Endogenous melatonin and Vitamin D3 via autophagosome production.
Back to the light story.
Cell-Cycle Checkpoints
The circadian clock regulates the timing of cell cycle progression, including the activation of cell cycle checkpoints. Key cell cycle regulators like cyclins and CDKs (cyclin-dependent kinases) are expressed in a circadian manner, coordinating cell division with the time of day.
For what purpose?
To minimize the risk of mutations during DNA replication.
Tumor Suppressor Genes
Tumor suppressor genes, particularly p53, are under circadian regulation.
The activity and stability of p53, often referred to as the “guardian of the genome,” vary throughout the day, optimizing its role in DNA repair, cell cycle arrest, and apoptosis according to circadian cues.
Immune Surveillance
The immune system’s activity, including the function of cytotoxic T cells and natural killer (NK) cells, is modulated by circadian rhythms.
Immune responses, such as cytokine production and the activity of immune cells, peak at certain times of the day, aligning with the body’s overall rhythm and optimizing the detection and destruction of potentially cancerous cells.
Antioxidant Defense Systems
Antioxidant enzyme levels and activity are influenced by the circadian clock.
For example, glutathione levels and the activity of enzymes like superoxide dismutase and catalase exhibit circadian variations, peaking at times when the body is more susceptible to oxidative stress, namely during the daytime when metabolic activity is higher.
Epigenetic Regulation
The circadian clock influences epigenetic modifications, such as DNA methylation and histone modification. The expression of enzymes involved in these processes, like histone deacetylases (HDACs) and DNA methyltransferases (DNMTs), can be circadian-regulated, impacting the timing of gene expression and maintaining genomic stability.
Hormonal Regulation
The secretion and activity of hormones like estrogen, testosterone, cortisol, and melatonin follow a circadian rhythm. These hormones influence cell proliferation, differentiation, and repair processes, with their circadian regulation helping to prevent abnormal cell growth that could lead to cancer.
Detoxification Systems
Liver enzymes involved in detoxification, particularly those in Phase I (e.g., cytochrome P450 enzymes) and Phase II (e.g., glutathione-S-transferases), are under circadian regulation. The expression and activity of these enzymes peak at certain times of the day, aligning with the body’s exposure to toxins. All to optimize detoxification.
Senescence
Cellular senescence is a state in which cells permanently stop dividing but remain metabolically active. This mechanism prevents the proliferation of damaged or aged cells that could become cancerous. Circadian rhythms influence the onset and maintenance of senescence by regulating the expression of senescence-associated genes and pathways, such as those involving p53 and p16.
Melatonin Production
Endogenous melatonin deserves its own spot. It has antioxidant properties and can inhibit cancer cell growth. It also enhances immune function and regulates estrogen production, both of which play roles in cancer prevention. Melatonin is a circadian hormone, through and through.
Angiogenesis Inhibition
Angiogenesis, the formation of new blood vessels, is necessary for tumor growth and metastasis. Circadian rhythms influence the expression of factors like vascular endothelial growth factor (VEGF) that promote or inhibit angiogenesis. The circadian clock helps to regulate the timing of angiogenesis, potentially limiting tumor growth by restricting blood supply during certain times of the day.
Metabolic Regulation
Metabolic processes are closely linked to cancer risk, as altered metabolism is a hallmark of cancer cells. The circadian clock regulates metabolic pathways, including glucose metabolism, lipid metabolism, and mitochondrial function. Proper circadian control of metabolism helps maintain cellular energy balance and reduces the risk of metabolic dysfunctions that can lead to cancer.
Mitochondrial Function
Mitochondria are light-sensing, circadian mechanisms. Mitochondrial dysfunction is at the heart of all cancer types through increased reactive oxygen species (ROS) and DNA damage, contributing to cancer development.
Circadian rhythms regulate mitochondrial dynamics (fusion and fission) and function, ensuring optimal energy production and minimizing oxidative stress, thereby protecting against cancer.
Gut Microbiota Regulation
The gut microbiota, which plays a role in metabolism, immune function, and inflammation, is also regulated by circadian rhythms. The composition and activity of gut microbiota fluctuate throughout the day, influenced by feeding times and the host’s circadian clock. A balanced microbiome supports overall health and reduces the risk of inflammation-related cancers.
“It’s noteworthy that the concentration of melatonin in the gastrointestinal tract surpasses blood levels by 10-100 times and there is at least 400 times more melatonin in the gastrointestinal tract than in the pineal gland.”
Hormone Receptor Sensitivity
The sensitivity of hormone receptors, such as those for estrogen, insulin, and glucocorticoids, varies according to the circadian cycle. This regulation ensures that cells respond appropriately to hormonal signals, maintaining growth control and metabolic balance, which are important for cancer prevention.
Autocrine and Paracrine Signaling
The circadian clock modulates autocrine and paracrine signaling pathways, which involve cells communicating with themselves or neighboring cells through secreted factors. These signaling pathways are important for maintaining tissue homeostasis and preventing aberrant cell proliferation.
Now do you understand why I push the circadian discussion towards the forefront of health, especially for the prevention of all chronic disease?
Cancer prevention necessitates circadian alignment with the light and dark cycle.
Toxic artificial light and non-native, man-made electromagnetic frequencies are pro-cancer environmental inputs.
An indoor lifestyle at the tune of 90%+ is pro-cancer.
Chronic Vitamin D3 and melatonin deficiency is pro-cancer.
Artificial light exposure after sunset is pro-cancer.
Sun-avoidance is pro-cancer.
Lack of melanin and melanin destruction is por-cancer.
As per the discussion of sunlight and skin cancer, understand that there’s a lot of complexity to this relationship.
One thing is certain:
Centralized medicine uses isolated UV light under artificially blue lit conditions on nocturnal, albino animals that are bathed in nnEMF to conclude that the “sun causes skin cancer.”
Melanoma is not caused by sunlight exposure, while squamous and basal cell have weak associations with it, especially when you consider the other circadian evidence on this.
The sun’s full light spectrum is designed to protect cells from cytotoxicity because red and infrared are the balancing forces to UV and blue light.
UV-A/UV-B and blue light also offer extensive benefit.
Read the article below for more on the relationship of cells to light.
If you learned something new here, share the article with your circle.
Much love,
Zaid
This is so comprehensive and succinct simultaneously! 🙌🏼
Sharing immediately so I can simply refer questions to this content.