@ Sydney Bright

Energy is at the root of life and nature. Life is a product of the energy flow from the sun to the earth, as a natural consequence of entropy and the second law of thermodynamics. When contemplating human health, one must similarly consider the fundamental role energy plays in our physiologic system. There are two major sources of energy to consider: the energy of the sun which gives rise to life on this planet, and the energy produced by our cells, in the mitochondria, in the form of Adenosine Triphosphate (ATP). Mitochondria, commonly known as the ‘powerhouse’ of the cell, was a symbiote that found its home within the proto-eukaryotic cell roughly 1.5 to 2 billion years ago1. This merger between two cells was developmentally significant, as it gave a cell the capability of producing energy internally, allowing for more complex processes. ATP is produced within the mitochondria via oxidative phosphorylation which includes two steps: the electron transport chain and chemiosmosis. The electron transport chain is where electrons provided by the glucose from our food, combined with the oxygen we breathe, produces a proton gradient across the membrane of the mitochondria, and results in the production of water. The proton gradient produced subsequently allows a protein complex named ATP synthase to produce ATP, the energy for the body. Up until very recently in human history, the most common cause of death was from diseases that were communicable. Given the rise of modern medicine, many of these diseases are treatable. However, in the 1900s, a shift also occurred where non-communicable disease because, by a large margin, the leading cause of death2. Leading causes of death today include diabetes, cancer, obesity, and respiratory disease2. Unlike our historical past, the way society alleviates this burden of disease is not by being hostile toward a pathogen, but by having humility in appreciating how our modern lifestyles are out of sync with nature and causes disease. For example, our modern lives create busy brains, and we accordingly lose appreciation for having a state of mindfulness, which is a state of mind more akin to life in nature which has the capability of reducing overall chronic disease3. At the physical level, what is at the root of our chronic disease is the health of our mitochondria. With energy, in the form of ATP, the body is not capable of effectively performing the physiological processes needed for healthy function. No matter how many good resources you feed a factory, without energy, there is no production. Mitochondrial health is at the center of our chronic disease4,5. The key to mitochondrial health includes some intuitive solutions such as exercise and good nutrition. However, to gain a deeper understanding of the deterioration of our mitochondria, one must appreciate this powerhouse’s relationship with the energy that feeds the planet. Mammal biology is adapted to live in the sun, and our physiology consequently requires a relationship with it. As discussed in a previous [piece](https://highlighter.com/a/naddr1qvzqqqr4gupzq422kmldvavct44endu667mcfluv5jjmqfmcsyhpj68wurrvhsn7qq29xet9942xsefdf35kw6r594nh2m35w9ss6u2jz6), there are many health benefits to the eyes and skin from both the longer-wavelength hours (red light) of the sunset and sunrise, and the ultra violet light of the midday. Our body benefits from the wide range of light emitted by the sun throughout the cycle of the day. However, we are similarly at a detriment if we receive a wavelength of light that is unnatural to that time of day. Light plays a predominant role in our circadian rhythm. Artificial light at night (ALAN) severely delay the production of melatonin, the hormone that helps us sleep6. This is caused from our exposure to blue light, which only naturally occurs during the midday, but is being emitted by nearly every electronic light source in our modern homes7. Made worse is the fact that LED screens emit 3 times more blue light than non-LED screens8. Our circadian rhythm and sleep health is also highly influential on our mitochondrial health. To explore this idea further, a more thorough understanding of mitochondria is needed. As mentioned previously, mitochondria fundamentally turn our food and oxygen into water and energy. This is done via oxidative phosphorylation. Figure 1 below provides a diagram for this process. Figure 1 Sourced from The Role of Mitochondria in Cancer and Other Chronic Diseases (Gonzales, 2014) In this process of oxidative phosphorylation, complex 1-4 perform the electron transport chain. Various processes occur that pump protons (H+) out of the mitochondria and into the cell, only so that the ATP synthase pump can produce ATP by moving the proton back inside due to the gradient formed on each side of the inner membrane. Complex I and II move protons provided by NADH and FADH from glucose. Complex IV does so by turning oxygen into water. This process of turning oxygen into water comes with a periodic side effect of producing reactive oxygen species (ROS). ROS can be beneficial to the body, but in can be dangerous in excess. Most critically, ROS can damage the mitochondrial DNA (mtDNA)4. Dysfunctional mtDNA will result in the improper production of proteins that are necessary for us to sustain life4. This naturally means that the body is constantly in a state of balance: both producing the necessity of ROS despite its damage to our mtDNA, while simultaneously performing processes that reduce this damage. Melatonin, an antioxidant produced via the circadian rhythm, is one such method of reducing this damage via the reduction of ROS9. A takeaway here is that a healthy relationship with sleep can directly benefit mitochondrial health. Additionally, healthy sleep is obtained by becoming more synchronized with the sun and reducing the amount of artificial blue light exposure during the times outside of the midday. Melatonin can also be increased with a meditation practise10. Furthermore, it has been shown that mitochondria themselves produce more melatonin than the pineal gland, for their own protection11. This further highlights the importance in mitochondrial health, as they need to be activated enough to produce more melatonin to prevent chronic issues. However, this is just scratching the surface of how we keep our mitochondria healthy. Sunlight is central to mitochondrial health. On the one hand, sunlight increases the production of melanin, the pigmentation that is responsible for darker skin. This is important because melanin protects our skin from DNA damage caused by UV light, and because mtDNA is also damaged by UV light, melanin likely offers safe protection for our mitochondria12,13. UV light also increases the activity of melanocytes, increasing the production of melanin and leading to darker skin13. This is especially true in the eyes, where it has been shown that UVB stimulation to the eye causes increased epidermal melanocyte activity14. This leads to the possible conclusion that sunglasses, which block UV rays from entering the eye, decrease our ability to produce melanin when we expose ourselves to the sun. It is common in the modern era to consider UV light dangerous, as its capability to damage DNA could lead to skin cancer. This is a drastically oversimplified rational. A study in 2014 known as the Southern Sweden Cohort aimed to investigate to what degree sun exposure led to increased death of pale individuals stemming from this rational15. The results found that increased sun exposure was extremely indirectly correlated with risk of death15. Meaning, the more someone was out in the sun, the less likely they were to die. The authors of this paper mainly attributed to the vital importance of Vitamin D production, but the benefits likely run much deeper. Consider how animals in the wild may bask in the shade during the middle of the day. Naturally, UV light has its costs and benefits, and avoiding the rays emitted in the middle of the day would be helpful. Nonetheless, these animals are outside all day, meaning they are also being exposed to infrared light (IR) which, like UV light, is not visible. IR light is highest during the midday as well, but it can pass through objects more easily due to its longer wavelength. Infrared light plays a key role in mitochondrial health and is something we severely lack from living indoors. IR light increases ATP production in the mitochondria. A recent study found that blood glucose spikes could be reduced when exposing patients to IR light16. Additionally, patients exhaled more CO2, a byproduct of oxidative phosphorylation and cellular respiration16. Both measurements indicate greater mitochondrial activity, driven by the exposure of IR light. There are several theories as to how IR triggers this incredibly healthy response. It is possible that Cytochrome C Oxidase, which transfers electrons between complex III and IV, is a chromophore for infrared light and increases its activity under its exposure, thereby allowing for the increased production of ATP17. It is also possible that the longer wavelength light increases ATP synthase efficiency by reducing the viscosity of the water surrounding the ATP pump18. Either way, there is ample evidence to suggest that our human body benefits directly from sun exposure. The light we receive from the sun passes into our bodies and increase the activation of our mitochondria, providing us with the energy necessary for a healthy life. Mitochondria benefit from sunlight beyond potential direct influences from the rays of light. Additionally, there is a relationship between UV light, melanin, and mitochondria. Proopiomelanocortin (POMC) is a precursor protein for many melanocortin, which include melanocyte-stimulating hormones (MSH), that produce melanin19,20. UV light is what triggers the production of the POMC-derived melanin producing hormone, which leads to the production of melanin itself21. All of this is to say that UV light leads to the production of melanin and the darkening of our skin pigmentation. Melanin, besides determining skin color, also plays an important role in mitochondrial health. Melanin, due to its chemical structure, is a reversible oxidation-reduction system, meaning it can go through both chemicals processes that allow it to lose and gain electrons22. This means that melanin can acts as a kind of battery, storing electrons for when they are needed. This is vital to mitochondrial health, because fundamentally what the electron transport chain needs to produce ATP is, obviously, electrons. The more melanin the body has, the more batteries it has to store electrons for use by the mitochondria. Therefore, there is a deep fundamental relationship between the body’s need to be exposed to the sun’s UV rays, and its ability to maintain melanin supply to fuel the electrons needed for mitochondrial ATP production. Lastly, it is then curious to consider how some of our ancient ancestors who lived in environments where the sun was not abundant were able to stay healthy, given the importance of sun exposure on mitochondrial health. To understand how populations in northern latitudes prospered, a thorough investigation of uncoupled mitochondria is required. Within some mitochondria are uncoupled proteins. These proteins allow the protons to re-enter the mitochondrial matrix without using the ATP synthase. Rather than generating ATP through this process, heat is generated instead. There are various kinds of uncouple proteins (UCPs)23: 1. UCP1 are mainly founded in brown adipose tissue (BAT) as is activated by fatty acids 2. UCP2 are found in the lymphoid system, macrophages, and pancreatic islets 3. UCP3 are mainly found in skeletal muscles When a mammal is exposed to repeated cold temperatures, this triggers the development of brown fat24. This development of brown fat from the cold was an evolutionary adaptation that seemed to develop independently in European and Asian people25. Furthermore, there is evidence to suggest that homo-sapiens acquired this adaptation through the interbreeding with Neanderthals and Denisovans respectively25. This suggest that the humans who left Africa, our birthplace with plenty sun exposure, were able to survive and thrive better if they received the genes of our cousins that had mitochondria more fit for the cold environments. Despite this adaptation for warmth, these uncoupling proteins do not explain how cold adapted humans were able to have proper mitochondrial health given the reduced sun exposure. Research has also found that increased heat dissipation by mitochondria coincides with an increased expression of the gene that encodes leptin26. Accordingly, the LEPR gene influences satiety, fatty acid processing in adipose tissue, energy balance, fat storage, and glucose metabolism26. Furthermore, leptin activates POMC27. Given POMC leads to the generation of melanin, a storehouse for electrons, cold adapted individuals were able to maintain proper mitochondrial health by producing melanin via a different mechanism than those who are exposed to the sun. This provides much perspective to those living in colder climates today, but who live in temperature regulated homes and do not regularly expose themselves to the cold. In summary, a proper relationship with sunlight is vital to mitochondrial health and reducing chronic disease. Overexposure to blue light decreases melatonin, which negatively impacts sleep and reduces our mitochondria’s ability to defend itself from the DNA damage of ROS. UV light is vital to the production of melanin which provides ample supply of electrons to our mitochondria so we can produce energy. Furthermore, infrared light allows for the mitochondria to be more efficient at turning those electrons into energy. Lastly, for human beings that do not live in sunny climates, exposure to the cold leads to the development of brown fat which contains within its mitochondria that will generate heat and melanin as a replacement for UV light. Nature is where true healing is found. References 1. Wallace DC, Brown MD, Lott MT. Mitochondrial DNA Variation in Human Evolution and Disease. Vol 238.; 1999. www.elsevier.com/locate/gene 2. O U AP, F UC, F EO, O C AC. Epidemiologic Transition of Diseases and Health-Related Events in Developing Countries: A Review. American Journal of Medicine and Medical Sciences. 2015;2015(4):150-157. doi:10.5923/j.ajmms.20150504.02 3. Zhang D, Lee EKP, Mak ECW, Ho CY, Wong SYS. Mindfulness-based interventions: An overall review. Br Med Bull. 2021;138(1):41-57. doi:10.1093/bmb/ldab005 4. Gonzalez MJ, Miranda-Massari JR, Duconge J. The role of mitochondria in cancer and other chronic diseases. Published online 2014. Accessed August 30, 2024. https://www.researchgate.net/publication/311389607 5. Casey M, Calley M. Good Energy: The Surprising Connection Between Metabolism and Limitless Health. Avery; 2024. 6. Phillips AJK, Vidafar P, Burns AC, et al. High sensitivity and interindividual variability in the response of the human circadian system to evening light. Proc Natl Acad Sci U S A. 2019;116(24):12019-12024. doi:10.1073/pnas.1901824116 7. West KE, Jablonski MR, Warfield B, et al. Blue light from light-emitting diodes elicits a dose-dependent suppression of melatonin in humans. J Appl Physiol. 2011;110(3):619-626. doi:10.1152/JAPPLPHYSIOL.01413.2009/ASSET/IMAGES/LARGE/ZDG0031194630004.JPEG 8. Cajochen C, Frey S, Anders D, et al. Evening exposure to a light-emitting diodes (LED)-backlit computer screen affects circadian physiology and cognitive performance. J Appl Physiol. 2011;110:1432-1438. doi:10.1152/japplphysiol.00165.2011.-Many 9. 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Ultraviolet B Irradiation of the Eye Activates a Nitric Oxide-dependent Hypothalamopituitary Proopiomelanocortin Pathway and Modulates Functions of α-Melanocyte-stimulating Hormone-responsive Cells. Journal of Investigative Dermatology. 2003;120(1):123-127. doi:10.1046/J.1523-1747.2003.12004.X 15. Lindqvist PG, Epstein E, Landin-Olsson M, et al. Avoidance of sun exposure is a risk factor for all-cause mortality: Results from the Melanoma in Southern Sweden cohort. J Intern Med. 2014;276(1):77-86. doi:10.1111/joim.12251 16. Powner MB, Jeffery G. Light stimulation of mitochondria reduces blood glucose levels. J Biophotonics. 2024;17(5):e202300521. doi:10.1002/JBIO.202300521 17. De Freitas LF, Hamblin MR. Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy. IEEE Journal of Selected Topics in Quantum Electronics. 2016;22(3):348-364. doi:10.1109/JSTQE.2016.2561201 18. Sommer AP, Haddad MK, Fecht HJ. Light Effect on Water Viscosity: Implication for ATP Biosynthesis. 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Sellayah D. The Impact of Early Human Migration on Brown Adipose Tissue Evolution and Its Relevance to the Modern Obesity Pandemic. J Endocr Soc. 2019;3(2):372-386. doi:10.1210/JS.2018-00363 26. Sazzini M, Schiavo G, De Fanti S, Martelli PL, Casadio R, Luiselli D. Searching for signatures of cold adaptations in modern and archaic humans: hints from the brown adipose tissue genes. Heredity 2014 113:3. 2014;113(3):259-267. doi:10.1038/hdy.2014.24 27. Oswal A, Yeo GSH. The leptin melanocortin pathway and the control of body weight: Lessons from human and murine genetics. Obesity Reviews. 2007;8(4):293-306. doi:10.1111/j.1467-789X.2007.00378.x