The Walking Dead but it’s Cell vs. Cell
A look into the science of aging.
“Commander, I have an urgent report!”
“What happened, Jules?”
“The zombies are closing in! You need to fight them off! You need to call backup or run. They are co-”
And boom, Jules just aged. The zombie took a nice bite out of her and she aged.
Wait.. what? You read that right. Everyday, our functioning cells try to fight off these ‘zombies’ in our bodies but ultimately, it is a losing battle because we continue to age. These ‘zombies’ are known as senescent cells and in order to achieve any semblance of immortality, we need to get rid of them.
🚨 But quick disclaimer, dying is inevitable. Our cells are programmed to die, so diminish any dream of becoming the next Hercules. However, we can delay the fateful event of dying.
Aging is Actually a Disease
It seems like a crazy idea but realizing aging is a disease is the first step towards extending the human lifespan. Not convinced? Let’s list what makes a disease, a disease:
✅ A condition that negatively affects the structure or function of all or part of an organism.
✅ It is not the result of any immediate external injury.
✅ Associated with specific signs and symptoms.
Looks like aging meets the disease criteria.
Start panicking, we all have it.
It’s not as if aging is some mystical phenomenon, there is actually science behind why you age and what happens when you do.
Happy Birthday, Congratulations you Aged
The verified oldest person on Earth lived to be 122 years old, that is a great deal of time. I’m sure you have been told to eat healthy and exercise a lot so you live for a long time, there is actually some truth to that. Average life expectancy varies greatly as a result of numerous factors including what you eat, exercise and where you live. Even your happiness levels can subtract or add years from your life. However, lifestyle changes can only do so much.
Aging introduces countless diseases and disorders into our bodies. You could argue the sickness is due to external factors but consider this:
Though smoking increases the risk of getting cancer fivefold, being 50 years old increases your cancer risk a hundredfold. By the age of 70, it is a thousandfold.
You can thank your lovely cells for this one. Every day, billions of your cells die to make room for new ones. While most cells can be easily and quickly reproduced, muscle and nerve cells can’t really be reproduced even though they last for a long time. They must be replaced by other cells. This race to replace cells is what makes the body weaker overtime.
The “Zombie” Cells
How come as we get older, we become sicker? One of the mechanisms behind this is the buildup of senescent cells. Your body is made up of trillions of cells that are constantly going through cell division and every time they divide, they make a copy of their DNA as well. The DNA is tightly packed into structures called chromosomes, however the problem is DNA replication is by no means perfect.
DNA replication skips over the ends of the chromosomes, to prevent important genetic information being cut out, our chromosomes have something called telomeres. You can think of them as those small plastic bits at the ends of your shoe laces.
After many rounds of cell division, these telomeres start to shorten and eventually disappear. Cell division stops once the telomeres shorten to a certain point, this stage is called cell senescence.
Cell senescence ensures there is no uncontrollable cell division, which is the cause of cancer. However, problems arise once these cells don’t actually kill themselves. Generally once a cell stops dividing, it loses its function and dies. Long-term senescent cells on the other hand stay in the body, functionless and not dividing, affecting the surrounding cells as well.
They are a nuisance.
Programmed Cell Death
Apoptosis, sometimes called “cellular suicide,” is a normal, programmed process of cellular self-destruction. Even though it involves cell death, apoptosis serves a healthy and protective role in our bodies. This is not to be confused with necrosis, which is the death of a cell as a result of an injury.
The tumour suppressor gene, p53 is a gene with a key role in apoptosis. The protein it codes for belongs to a family of proteins that has three members: P53, P63 and P73. All of them have about 60–70% amino-acid identity of the DNA-binding region and all three can induce apoptosis. This is an important bit of information to note.
Cells don’t just randomly decide they are going to be long-term senescent cells and refuse to die, senescent cells generally have a lack of the proteins mentioned above, P53, P63 and P73. This means programmed cell death doesn’t become triggered, therefore leaving the zombie cell to fester.
Aging isn’t something you should just accept. Why live for 80 years when you can live for 110 with the same health as when you were 20?
That’s right, it’s possible. Maybe we can help out Jules! ;)
Extending the Human Healthspan
Aging is no longer unchartered territory. Longevity research has made some huge advances in the last few years as scientists have begun to understand the mechanisms behind aging and how to manipulate them.
Yes, a large focus is to extend life spans, however much of the current research in longevity is to optimize healthspans, living healthy for longer.
One key aging treatment includes senescent cell removal.
I believe that aging is a disease. I believe it is treatable. I believe we can treat it within our lifetimes. And in doing so, I believe, everything we know about human health will be fundamentally changed.
- David Sinclair
Targeting Senescent Cells
Short-term (acute) senescent cells are associated with positive effects. Once they have completed their job, immune cells are recruited to remove them. In contrast, long-term (chronic) senescent cells are associated with disease as they secrete pro-inflammatory and pro-tumorigenic factors in a state known as senescence-associated secretory phenotype (SASP).
In other words, acute senescent cells = good & chronic senescent cells = bad.
Current chronic senescent therapies function in three main ways:
- Use of senolytics.
- Inhibition of SASP.
- Strengthening the immune system (immunosurveillance).
Let’s take a brief look into each one.
An option to eradicate the negative effects of chronic senescent cells is to kill them, specifically using compounds called senolytics. Routinely administration of the drug kills senescent cells that are generated in the tissues, and the immune system is responsible for clearing apoptotic (dead) bodies.
In a small clinical trial, Mayo Clinic researchers demonstrated for the first time that senescent cells can be removed from the body using drugs they named senolytics. The result was verified through blood as well as changes in skin and the number of senescent cells in fat tissue.
The trial involved participants who had diabetes-related kidney disease and was the second clinical study of senolytics to be published by Mayo, but is the first trial to show that senolytic drugs can remove senescent cells from humans as they did in numerous studies in animals.
For three days, the nine human participants received a dose of dasatinab and quercetin combined. Though the drugs cleared the body in a couple of days, the effects on reducing senescent cells were evident for at least 11 days afterwards. The researchers say this shows the senolytic drug combination significantly decreases senescent cell burden in humans.
“This small-scale clinical trial is a significant step forward for translation of senolytic therapies.”
- Ronald Kohanski
Senomorphics is another strategy to restrict the functions of senescent cells through the specific silencing of SASP. It’s a complex mixture of soluble components including cytokines, chemokines, growth factors, proteases and angiogenic factors that mediate the signalling functions of senescent cells.
There has been evidence that the buildup of SASP-positive senescent cells can result in age-related conditions including inflammation. This leads scientists to believe silencing SASP will alleviate these effects.
The first step demonstrates treatment with senomorphics to restrict SASP factors in senescent cells. Over time, the treated cells will be removed by immune cells. Finally, a regenerative process will lead to normal tissue functions, essentially restoring the normal cells.
Okay, so far we have drugs that can kill the senescent cells and targeting the negative parts of the senescent cells. Anything else?
No, Jules isn’t going to eat a bunch of broccoli and look 20 again. This method is like a senescent cell surveillance system in your immune system, it’s called immunosurveillance. A very creative name indeed.
BIG IDEA — Target senescent cells to strengthen the immune system for efficient recognition and elimination of these cells.
The role of the immune system in the elimination of senescent cells is fundamental as a decline in immune function is directly related to an increase in the number of senescent cells and finally, the development of disease.
This treatment has two approaches:
- Improving the specific anti-senescent cell functions.
- General enhancement of immune functions.
Sounds pretty good, how does it work?
This strategy is similar to SASP inhibiting however, there is the additional step in the targeting of senescent cells.
In step 1, there is additional immune cell support in order to kill the senescent cell. Then, the improved immune system targets senescent cells, leading to their removal. Next, a regenerative process will maintain normal tissue functions.
The Ethical Debate
Boo, ethics may be irritating however they are the key reason why our society has some peace and order.
There is huge ethical debate on whether or not we should even be increasing lifespans. One key argument is amplifying the already existing “unequal death.”
The upcoming treatments will widen the bridge between the poor and the wealthy. The figure speak for themselves. In many African countries south of the Sahara, life expectancy is less than 40 years, whereas the average lifespan in rich and developed countries is 70–80 years.
Even at a smaller scale, will treatments only be accessible for upper-class individuals and out of reach for the middle class?
My Thoughts
Everything starts off as expensive, especially technology.
However, there have been countless cases where the expenses eventually drop to an affordable range. Yes, at first this “unequal death” will be of significance, but once the treatment becomes more normalized and accepted, the cost attached to it will become smaller.
Imagine a world where you go to the doctor’s for your seasonal check-up and part of that check up was casually getting your chronic senescent cells removed too?
I believe it is possible, and once it happens, it will be revolutionary.
“Hey Jules, you’re going to be alright. Just make sure to go to your senescent check-up tomorrow.”
“You got it commander, now let’s beat up the rest of these zombies.”
Further Reading
- Science of Aging
- Mayo Clinic
- More Treatment Possibilities
- A Deeper Look into the Ethics
- Longevity Companies
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