Mighty Mitochondria

One very small part of our bodies, found in every one of our cells, has a special need for nightly cleaning and maintenance: these are the engines that drive every cell, our mitochondria. These bacteria-like organelles (organ-like cell parts) perform the final stage of “burning” raw material such as sugars (etc), in order to produce our real fuel: ATP, (adenosine triphosphate). I'll explain roughly how ATP powers everything our bodies do in a moment, but for the moment it should be noted that mitochondrial dysfunction (and even death) is a very plausible consequence of insufficient darkness. When mitochondria are asked to keep going at daytime rates for longer than twelve or thirteen hours without garbage collection and repair and then subjected to shortened nights with less melatonin available over a shorter time, ongoing damage to our mitochondria from free radicals becomes more and more likely. “Free radicals” are the waste products that occasionally form during the chemical reactions mitochondria perform to make and activate ATP. They can combine actively with other molecules and introduce random changes – not the sorts of things one wants hanging around the delicate cellular machinery. As well, other dangerous “reductive oxygen species” formed during daytime by exposure to ultraviolet light, inhaled particles from vehicle exhaust, etc, need to be cleaned up, and melatonin is natures first line of defense here too. All these dangerous reactive molecules pose a general threat to cells, collagen, and mitochondria, and the damage from them easily accumulates over time. It should be no surprise then, that

“alterations in oxidative phosphorylation [mitochondrial function] are characteristic of type 2 diabetes, Parkinson disease, Huntington disease, and other diseases.”

It might be supposed that this is due to genetic differences re our mitochondria. But research (as of July 2006) says otherwise:

“we evaluated the complete set of common mtDNA variants for association with type 2 diabetes in a sample of 3,304 diabetics and 3,304 matched nondiabetic individuals. Association of mtDNA variants with other metabolic traits (body mass index, measures of insulin secretion and action, blood pressure, and cholesterol) was also tested in subsets of this sample. We did not find a significant association of common mtDNA variants with these metabolic phenotypes. Moreover, we failed to identify any physiological effect of alleles that were previously proposed to have been adaptive for energy metabolism in human evolution.” [16773565]

At least some genetic variations have been tied to Parkinson's disease, which are otherwise rare variations in mitochondrial genes: specifically in mitochondrial cytochrome b variants N260D and G251S. [12391595] This again suggests a connection between mitochondria and chronic illness: note that we should expect that some variations in genetic heritage, that affect mitochondria, will cause especially difficult problems under unusual environmental conditions that affect mitochondria, such as excess exposure to artificial light.

There is also another reason to suppose that short nights can greatly reduce mitochondrial efficiency. It has been suggested that mitochondria reproduce themselves during darkness [FOOTNOTE: Mitochondria may once have been bacteria which were symbiotically absorbed by animal cells in the distant evolutionary past. Although also part of our cells, they have some of their own DNA and reproduce themselves. Mitochondria can only multiply with the help of the rest of the cell, however. Many of “their” genes are part of the nucleus of the cell that contains them. Mitochondria are therefore unable to reproduce outside human (or other animal) cells. Since most of the DNA mitochondria depend on are part of the cell nucleus, research hasn't yet eliminated the possibility that genetic influences on mitochondrial function strongly influence metabolic diseases, but this certainly looks unlikely now.] rather than during the day when they're especially busy producing energy for our activities. [15506520] It is reasonable to guess, therefore, that if we shorten our periods of darkness day after day for years and decades on end, we might end up with fewer and older mitochondrial energy engines, in poor repair within each of our cells. Reduced energy/ATP production would be an entirely predictably result.

Certainly, whether as a result of accumulated damage from free radicals (which has been suggested as the primary mechanism of aging) or eventually having far fewer mitochondria; either fewer or less efficient mitochondria constitute a metabolic problem. That is, we will not have enough ATP fuel available to get everything done that ought to be done. For example, making glycogen whenever desired (when blood sugar levels are high.) If cells are not able to make glycogen when requested by insulin to do so; this constitutes “insulin resistance”, which is the root of diabetes type 2, a large part of “metabolic syndrome”. Metabolic difficulties would seem to be an entirely predictable result of this chain of events begun by exposing ourselves to far more light than nature intended. Our cells may only contain enough healthy mitochondria to give us a proper amount of energy if we are getting enough darkness, something that can't now happen by accident in the modern world.

The most predictable consequence of short nights and sleeping into the light, therefore, may be the appearance of diabetes together with the other consequences of metabolic syndrome: obesity, hypertension heart disease, and according to recent research on metabolic syndrome, Alzheimer's too. While the suggestion that excess light exposure might be the reason why mitochondria are helping cause human illness is new, being first published at Photoperiod Effect.com in September of 2006; it is now well accepted that mitochondrial dysfunction helps cause disease: “During the past 10 years, it has become increasingly clear that this organelle contributes to a variety of human diseases, including cancer, diabetes, obesity, neurodegeneration, and aging.” [http://www.broad.mit.edu/mpg/people/vmootha.html] Moreover it has been suggested that melatonin, which is controlled by light exposure, is linked to mitochondrial function: “Interactions between melatonin and NADH may be implicated in mitochondrial metabolism.” [16098097] By tracing gene expression in diabetics – that is, what genes are actually being used to create proteins - diabetes has now been specifically tied to variations in mitochondrial function. Researchers identified “...a set of genes involved in oxidative phosphorylation [that is, connected with ATP production by mitochondria – RJ] whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal...” [12808457] Moreover, a very early sign of diabetes is the prevalense of the very sort of ROS (free radical-like elements) that melatoin are supposed to protect mitochondria against, by cleaning them up during darkness:

“These findings suggest that total plasma lipid peroxidation is increased in insulin-resistant individuals at an early, preclinical stage, ie, well before the development of glucose intolerance and type 2 diabetes.” [10966898]

Even the “other possible pathways” by which excess light could cause illness that I'll describe later, such as collagen disorders, may turn out to be more or less dependent upon the absence of sufficient available metabolic energy with which to perform important bodily functions; rather than genuinely independent pathways to disease.

Any significant reduction in the energy, the ATP, available to power bodily processes can have very widespread effects, including effects that are not easily forseen, particularly if this relative shortage persists over the long term. For example, metabolic problems resulting from mitochondrial dysfunction as a result of long days can certainly be expected to hamper our immune systems: these take great amounts of energy to run, and notoriously, are sharply cut back during periods of starvation. For an effective immune response to be mounted, cells and antibodies must be made, whatever is destroyed must be thoroughly cleaned up, etc. If our body's energy economy is in trouble, we will not be able to devote such large amounts of energy even to the effort to protect ourselves against possible threats to our health in the near future.

However melatonin, and prolonged periods of true darkness, does much more for us than clean up free radicals, as important as this function is. Very importantly, most medical researchers now agree that our immune systems experience a profound daily cycle largely driven by melatonin (but not wholly – see the FAQ document question 20.) In some ways, this nightly change in our immune system is a decline: some steroids that speed urgent kinds of healing are withdrawn, etc. But in far more ways the evidence shows that our immune systems ramp up and peak at night – for example cytokines are released that control inflammation and immune reactions but which would slow us down during the day if they were present in the same quantities. It would seem that while much of our available energy is reserved, during the day, for activity, whereas, at night, more energy and resources are devoted to identifying and tackling both infectious illness, and at least some inflammatory and healing tasks.