Thursday, November 14, 2013

How free radical formation and mitochondrial dysfunction can speed up the disease process

When you look at most of the diseases we see today, many share a few things in common.  Schizophrenia, Alzheimer's disease, Pakinson's disease, epilepsy, migraines, cardiovascular disease, diabetes, neuropathic pain, fibromyalgia, Huntington's disease, and cancer are all diseases that share three common threads.  Every one of these conditions, and even the process of aging itself, is associated with high free radical production, mitochondrial dysfunction, and inflammation(1, 2, 3).  In this blog we will discuss how these three phenomena work synergistically to take you down.

Free radical damage to cells

As discussed in my last blog, mitochondria are little organelles within your cells that are responsible for generating the bulk of your energy needs.  I also discussed how, as a natural byproduct of energy generation through the electron transport chain of the mitochondria, some free radicals are produced.  Free radicals, or reactive oxygen species(ROS) are molecules that have an unpaired electron in their outer shell.  Free radicals are very reactive, and since they are unstable until the unpaired electron finds a partner, they go around to other parts of the cell and try to steal an electron, turning that molecule in to a free radical.  It is important to note that this reaction isn't simply with free molecules that are floating around in your cells, free radicals interact with molecules that make up the machinery of your cells.  Obviously, if you want your cells to function properly, you want to keep free radicals from getting out of hand.

DNA and free radical damage

One of the problems that you run in to when free radicals get out of hand is the potential for the free radicals to alter the mitochondrial DNA.  Every one of our cells has 2 types of DNA, nuclear DNA and mitochondrial DNA.  The DNA most of us is familiar with is the nuclear DNA.  Both types of DNA contain instructions for building you, but 99.9999999% of those instructions are found in the nuclear DNA.  When your cells divide to form new cells, the nuclear DNA splits in to 2 and replicates to form a set of instructions for each cell.  If there is damage to the nuclear DNA, this can lead to copy errors which leads to unhealthy, irregular cells.

Certain types of radiation can cause damage to the nuclear DNA.  However, the nuclear DNA is surrounded by a membrane that protects it from other parts of the cell, so it probably doesn't get damaged directly by free radicals generated by the electron tranpsort chain in the mitochondria until you are producing huge amounts of them.  Since the mitochondrial DNA is within the mitochondrial membrane and is not separated from other parts of the mitochondria by a membrane, free radicals generated by the electron transport chain are free to react with the mitochondrial DNA.  While most of the important instructions are contained within the nuclear DNA, the mitochondrial DNA is mostly instructions for proteins contained within the electron transport chain.

Accumulation of free radical damage and mitochondrial dysfunction

Perhaps as free radical damage accumulates to the mitochondrial DNA, a tipping point is reached and the DNA is damaged to the point that new mitochondria made from this damaged mitochondrial DNA are dysfunctional and contain a poorly functioning electron transport chain.  This causes the generation of more free radicals leading to an environment of high free radical production and mitochondrial dysfunction.  In fact, there is scientific evidence that damaged mitochondrial DNA and a dysfunctional electron transport chain both lead to an increase in free radical production(4). As free radical production increases, so does systemic inflammation as free radicals activate genes that produce inflammatory cytokines(5).  What's more, since most of your cells contain many mitochondria(up to 2000 in liver cells), having many dysfunctional mitochondria can produce a large amount of free radicals that could eventually destroy the membrane surrounding the nuclear DNA and cause damage to it.

Keeping excessive free radical production at bay

While we cannot say for sure whether an environment of high free radical production, mitochondrial dysfunction and inflammation causes disease or that disease causes this environment, we do know for sure that this environment is not beneficial in any way to you or your cells.  If your goal is to be healthy, you should make it a point to limit excessive free radical generation by reducing the amount of energy going through your mitochondria and making sure your endogenous antioxidant defense system is generating antioxidants to help keep free radical production under control.  The easiest way to both of these things is to not over-consume calories and to get regular physical activity throughout the day, which is probably why doing both is associated with good health and a lower risk of most disease states. In fact, one could make the argument that there is a single general disease state in chronic disease, with each one of us being susceptible to different diseases based on our individual genetic code.