What causes aging? This is a question that has been answered by quite a couple of theories. However no theory has ever been approved because no one has ever been successful in reversing aging in human beings. The latter statement is however changing quite fast as many scientists working together are now attempting to reverse aging.
But enough about theories, we have a multitude of evidence to believe that what causes aging stems from our genes. Dr. Michio Kaku likes to call genes our “user manual”. So why do we believe that our genes are responsible for aging and how can we prove it; in other words what is our rationale and where is our evidence?
A short Analogue
I believe we all understand better when we can relate the information we get with real life situations. Imagine you have a mansion but you are always busy at work. So you hire a butler to be in charge of the house on your behalf. The butler cannot do all the maintenance work in the house so he hires 5 workers: a dishwasher; laundry worker; farm keeper; house cleaner; and a cook. These workers are under the control of the butler and not you.
For a while everything is fine in the house. During the day you are always away due to your busy career, but whenever you come home at night you always find the house is clean, dishes and laundry are done and everything is in order. You never really need to check on the butler because you can see there is nothing to complain about.
A couple of years later however, you come from work earlier than usual and you notice the farm is full of weeds. Hmmn you are tired and ignore it, besides you can always get fresh fruits and vegetables from the market. The next day the dishes from the previous night are still dirty. Well you had already eaten outside with friends and this is not a big deal, so you get your tired self to sleep.
A couple of weeks down the line, you now need clean laundry and you realize the laundry has also not been done all this time and all your clothes are dirty. You also realize that the house too has a bad smell because it has not been washed. Owk this is now getting out of hand and you look for your butler. After looking all over your big mansion you finally find him in a servant’s quarter outside the mansion. You are shocked however to find that he became cripple, blind and deaf. He can no longer control or communicate with the workers and they all left. You have no idea how he became this ill, he is still breathing, but having a really hard time surviving.
What Has This Got To Do With Aging?
The mansion is a cell in our body. The workers are proteins that have to keep the cell functional by maintaining it through biochemical process such as energy provision, degrading misfolded proteins to prevent them from accumulating in our cells; neutralizing reactive oxygen species; and etc. The butler is our DNA responsible for producing (encoding) all these proteins.
Every day our DNA gets damaged more than a million times depending on very unique factors for every individual. However don’t panick yet because our DNA is capable of dealing with its own damage while still maintaining the house. The DNA repairs its own damage in a process known as DNA Damage Response (DDR). For any type of damage there are 5 major mechanisms of repair. These include:
- Base Excision Repair (BER)
- Nucleotide Excision Repair (NER)
- Mismatch Excision Repair (MMR)
- Double Strand Break Repair (DSBR)
- Interstrand Crosslink Repair (ICR)
DNA damage happens randomly due to so many factors including replicative errors in mitotic cells, oxidative stress, some environmental chemicals etc. As such DNA damage is said to be stochastic. However as we have said DDR always comes to the rescue; UNLESS the genes that code the proteins used in DDR pathways also get damaged.
Therefore for instance if the pathway for BER is dysfunctional due to an abasic site on a base excision repair gene, BER will not be triggered. In essence damage to a repair gene whose nature subjects it to be repaired by the same repair gene will go unrepaired. At the same time if the same damage befalls any other gene (not necessarily a repair gene) it is will also go unrepaired. Abasic sites can therefore occur anywhere anytime from then on because they are left unchecked.
In short when our repair gene gets damaged who repairs the repair gene? And that is where damage starts accumulating. From our analogue we can see it as all house maintenance chores are not done and the house is unbearable. But the chaos stems from a dysfunctional butler. However it’s not the whole butler who is dysfunctional, just the eyes, ears and legs. If we correct/cure the butler he can go back to maintaining our mansion.
In our aging case, repairing not just any genes but the repair genes will get the cell up and functional again. This is because the repair gene will now be able to repair other genes whose damage it is programmed to repair. Quite a bold statement huh? The genetic theory of aging proves that compromising only these specific repair genes results precisely in the aging phenotype.
So Where Is The Evidence?
Remember the DNA repair mechanisms that we mentioned above? Let’s see what happens if any of these repair mechanisms are removed, will it result in only one disease such as cancer, or anemia, or is it precisely the entire aging phenotype if any repair pathway is compromised (1)?
What causes aging? Aging is caused by a malfunction or damage to our repair genes. Metabolic pathways responsible for maintaining our cells are then compromised and we start accumulating damage. Consequently we see this damage as accumulation of senescent cells; intracellular and extracellular waste products; abnormal cells such as cancerous cells; death of cells in very crucial post mitotic tissues; age related diseases;etc. Trying to deal with these damages does not deal with the root cause of the malfunction. It will be like trying to maintain the mansion in our analog while still keeping up with our very busy career? It can work but at a huge cost.
So in short to answer this question is one simple logic: damaged DNA is repaired using proteins from specific repair genes, however when repair genes get damaged who repairs the repair gene?
To understand this better you need to understand the basic scientific terms so that you can for instance be able to differentiate the DNA, a gene or the genome from each other. You also need to understand the role of the mitochondria DNA in aging and how reactive oxygen species (ROS) cause oxidative stress to DNA damage. All this has been researched and compiled for you on RESEARCH SERIES 1. Buying any of our research series not only keeps you updated with our research but also funds us to make aging reversal a reality.