Aging: Production of Free Radicals by Mitochondria

In each cell, thousands of little "power plants" known as mitochondria are hard at work. These mitochondria produce ATP(Adenosine-5'-triphosphate) which is essentially what powers our bodies. The production of ATP works by stripping electrons from the molecules, which then power the mitochondria's "turbines." Protons are then fed through the turbines and ATP is produced. The electrons are then sent to an oxygen molecule, which removes four electrons at a time. Once in a while, the oxygen molecule may receive an extra electron or two, making it chemically unstable and forming what is known as a free radical. These free radicals cause oxidation and try to steal electrons from other molecules, which leads to a chain reaction of issues. Since the free radicals are produced so close to the mitochondria, the mitochondria's DNA is sometimes mutated, which corrupts the mitochondria. These mutated mitochondria then no longer produce free radicals and are then not signaled for destruction by lysosomes.

This creates the first issue. How do you prevent the oxidation which is occurring by the production of free radicals? Obviously, the first solution that comes to mind are antioxidants. But antioxidants don't work too well since they lead to oxidative stress and can make cancer cells resistant to chemothearpy. Oh, and did I mention that only 1% of mitochondria's are actually mutated? So now you are probably wondering, how can 1% of these randomly occurring events lead to overall aging? The answer is LDL.

LDL(Low-Density Lipoprotein) is a bad type of cholesterol(which I shall discuss later). Cholesterol, is an important aspect of metabolism and is responsible for strengthening a cell's and/or a mitochondria's membrane. While these LDL pass by mutated mitochondria, they are attacked and mutated by free radicals. The LDL cholesterol then travels to the rest of the body, infecting a large amount of area and eventually becomes evenly spread throughout the body. So, how can we prevent all of this?

Well, you can't simply mess with mitochondria since they are a major aspect of metabolism and interfering with the process of metabolism leads to more severe issues. You can't simply destroy the mitochondria since that would destroy muscle fiber and interfere with the bodies skeletal muscle. The best bet? A treatment known as Allotopic Expression.

Allotopic Expression is the inputting of copies of the mitochondria's DNA inside the cell's nucleus. Mitochondria are one of a handful of cells which contain their own individual DNA. Injecting the mitochondria's DNA inside of the cell's nucleus would allow for the mitochondria to be properly rebuilt if it ever became mutated by free radicals. There are two known issues with Allotopic Expression though.

The first issue is that the DNA sequencing of the 13 proteins that make-up the mitrochndria's DNA are a different sequence than the cell's DNA, which is called code disparity. This can easily be fixed by swapping the "A's" to "B's", and the "B's" to "C's."

The second issue is that the 13 proteins that make-up the mitochondria'a DNA are highly hydrophobic and, when introduced to water, they curl up. This makes it impossible to extract them through the TIM/TOM(Tansporter Inner Membrane/Transporter Outer Membrane) of the mitochondria. This can be solved by trying to find other sub-species in which evolution has solved the issue of hydrophobia. Luckily, scientists have found a species of algae which has figured out a way to make 3 of the proteins for its mitochondria's DNA unhydrophobic. We can either search for the last 10 proteins in other sub-species, or we can take matters into our own hands with inteins. Inteins are sequences which tell a protein what to do and could tell the proteins which are hydrophobic to break into two small pieces, and then reassemble once they exit the TIM/TOM. The only issue with this is the inteins could be sequenced wrong and have the protein join back together inside of the TIM/TOM, causing excessive damage to the mitochondria.

Allotopic Expression seems to be the best bet to prevent the excessive damage caused by free radicals. It is estimated by Dr. Aubrey De Grey that Allotopic Expression can increase the human lifespan by 50%.