WHY TAKING ANTIOXIDANTS ORALLY IS BAD MEDICINE

Free radicals and reactive oxygen species (ROS) in particular play an important part in aging because they direct repair and regeneration and taking antioxidants ruins this endogenous signal. Free radicals are (usually small) molecules lacking an electron needed for stability; they will steal an electron from the first thing they bump into. Like pulling a cog out from clockwork, stealing an electron from a protein or enzyme is usually not good for the finely-tuned biochemical machinery of our cells. The free radical might be rendered safe in the process, but it has left some form of chaos and damage in its wake.

Free radicals are sufficiently dangerous to biochemical machinery that some of our body's defenders use bursts of free radicals as a kill mechanism.  That is why Denham's belief has died too slowly.  Science changes though as data comes in.

Scientists now generally concur that accumulated damage throughout the body due to free radicals is one important root cause of age-related degeneration - but the devil is in the details. The vast, overwhelming majority of those free radicals are generated by your own metabolism as an unavoidable byproduct. The rate of free radical generation increases greatly with age as the basic mechanisms of your metabolism are themselves damaged by the free radicals they created. This is not a one-step process, however. I've tried to walk through it at a high level at my blog, cribbing from the mitochondrial free radical theory of aging that was proposed by Wallace and working its way into general acceptance because of new data

Within each of your cells are many mitochondria, tiny biochemical power plants that convert chemicals from food to ATP, the basic fuel molecule used by your cells to provide energy for life.  

You have to beware of people who take advantage of the antioxidant theory of aging and have no earthly idea of how mitochondrial creation of free radicals really works.  This is why supplement makers and coffee makers are pushing the false narrative that antioxidant use is wise.  Marketing is legalized lying.  

Mitochondria were once a separate organism that came to live in symbiosis with ancestral cells. As such, they brought their own DNA to the party; some of it still remains within our mitochondria, separate from the DNA we carry in chromosomes in the cell nucleus.

Mitochondria have a couple of ways of generating ATP. The more efficient of these methods - oxidative phosphorylation (OXPHOS) - generates some amount of free radicals as a natural byproduct, and requires the proteins coded in the mitochondrial DNA to function. It is the predominant way by which healthy cells generate their power.

Free radicals created through OXPHOS within a mitochondrion are most likely to damage that mitochondrion; they're very reactive, so they won't get far before sabotaging something. The components that really matter are (a) a membrane that helps organize the movement of various chemicals in the process of generating ATP, and (b) the mitochondrial DNA.

Sufficient free radical damage to mitochondrial DNA shuts down OXPHOS within that mitochondrion, as the necessary proteins can no longer be produced. The mitochondrion switches over to using a less efficient method of producing power, one that doesn't produce free radicals but has to run at a much higher rate to produce the same level of ATP.

Mitochondria, like most cellular components, are recycled on a regular basis. Components called lysosomes are directed around the cell in response to various signals, engulfing and breaking down damaged or worn components. After the herd has been culled, surviving mitochondria within a cell divide and replicate, much like bacteria, to make up the numbers.

The signal to break down a mitochondrion is triggered by sufficient damage to its membrane: a sign that it's old, leaky, inefficient and needs to be replaced with a shiny new power plant.

BUT: if a mitochondrion has had its DNA damaged to the point of stopping OXPHOS/beta-oxidation/alpha-oxidation, it will no longer be producing NORMAL free radicals that can damage its membrane. So it will never get broken down by a lysosome. When the time comes to divide and replicate, it will replicate its damaged DNA into new mitochondria and disease is spread like a bacterial infection in your tissues. None of those new mitochondria will be producing free radicals via OXPHOS, and so will not be recycled either (autophagy).

One DNA-damaged, non-OXPHOS mitochondrion will eventually take over the entire mitochondrial population of a cell in this way. At that point, the trouble really gets started.

By the time you hit late life, perhaps 1% of your cells are in this state of being taken over by non-OXPHOS mitochondria. As for any neighborhood or city, it only takes a small proportion of dangerous criminals to make life really unpleasant for the rest of us.  Same true here at the tissue level.

Non-OXPHOS mitochondria have the unfortunate effect of depleting a needed molecule used in many cellular processes, NAD+. This is a carrier molecule in the OXPHOS process, given an electron (and turned into NADH in the process) to port between point A and point B within the mitochondria. Once the electron is delivered, the NADH becomes NAD+ again. But without a working OXPHOS process to return NAD+ into circulation, the cell would quickly build up a deadly excess of NADH, run out of NAD+ and hypoxia occurs and cells die. (Sinclair, 2013)

Fortunately for the cell, and unfortunately for us, there is another way to recycle NADH into NAD+. Since NADH is just NAD+ with [amongst other things] an electron stuck to it, all the cell has to do is export those unwanted electrons to other proteins via the Jablonski diagram I have posted over and over.

In the points above, I omitted details of the reaction that transforms NAD+ to NADH in order to focus on the electron that is ported around. Wikipedia gives an introduction to the full picture, which also involves an extra hydrogen atom (non-deuterium) - NADH is NAD+ with the addition of a hydrogen atom (one proton, one electron), and an additional electron. Nonetheless, it is the shuttling and exchange of electrons that is important here.

In a form of chemical waste dumping, this is just what the cell does. Structures on the cell membrane known as the plasma membrane redox system (PMRS) export electrons from NADH, recycling it into NAD+. This process is only very active in cells that have been taken over by DNA-damaged, non-OXPHOS mitochondria, but their outer surfaces are little hotspots of electron dumping.

What do these electrons do? Well, for one, they combine with oxygen molecules - which are abundant in any of our living tissue - to create reactive oxygen species (ROS): more free radicals. Sick cells have pseudohypoxia to limit the damage and try to survive as autophagy is defective.  This causes organ failure.  So you have the Rube Goldberg system outlined above whereby a few free radicals have caused a cell to become an ongoing, major exporter of free radicals into the surrounding environment. These will make life unpleasant for surrounding cells, but that is most likely not the real problem. ROS just can't travel far enough to explain how a corrupt 1% of our cells can cause a large fraction of the difference between being young and being old.

A more likely target for all the newly created ROS is cholesterol. Cholesterols, such as low-density lipoproteins (LDL) are used everywhere in the body and travel widely. If ROS reacts with nearby LDL - and there will always be nearby LDL - to form damaged, oxidized cholesterol, that damaged cholesterol can then be incorporated into and further damage biochemical processes throughout the body. For example, its effects on our arteries is well known:  What is not well known is how the light that excites that electron damages cholesterol rings by how it is programmed.  If the right frequency of light is on the electron cholesterol works well......if not you get a disease. 

In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma formation in the walls of arteries, a condition known as atherosclerosis, which is the principal cause of coronary heart disease and other forms of cardiovascular disease.

There are many other ways in which accumulations of oxidized cholesterol can send biochemical processes awry. This, then, seems to be a good candidate for the plausible, systematic method by which a small number of cells can work such varied damage upon your entire body.  Mitochondrial damage acts just like an infection does at the tissue level.  Aging does the same.  This is why health is the slowest form of death we chose by using the right light that excites electrons.  Mitochondria deal the right electrons to the right tissues to build health.