Stem Cells, CRISPR, and How to Literally Live Longer
In the year 1900, life expectancy of an average American male was around 45 years old. A little over a century later, an average American male can live a life of around 80 years, or a 77% increase. What makes the change so profound?
Longevity has been a baffling subject for centuries, from 16th century Ponce de Leon searching for the fountain of youth, to early alchemists trying to procure the elixir of life. And who wouldn’t want to live longer? And why do we already live so much longer than people only a mere 100 years before us? The answer lies partly in quality of life, but more in telomeres, stem cells, and free radicals among other things. Let me tell you how you can live longer.
Telomeres
The first step to understanding the secrets of longevity lie in useless bits of DNA called telomeres. Your body is made up of trillions of cells that keep dividing. Every time they divide, they make a copy of their DNA, which is tightly packed into chromosomes of which a normal person has 23 pairs of. However, DNA replication has errors. Sometimes, replication skips over the ends of the chromosomes, so important information could be cut out just like that. That’s where telomeres come in. Your body doesn’t really care if telomeres don’t get copied, because they’re well, useless.
Telomeres are essentially like aglets, the plastic caps at the end of your shoelaces to make sure the actual laces don’t get damaged. However, this protection only lasts so long. After a certain number of cell divisions, the telomeres become so worn down that they practically don’t offer any more protection. At this point, that cell stops dividing.
The casual layman may ask:
“Well if telomeres are good, why don’t we just make some elongated telomere technology or some thingamajig that makes it so telomeres never get shorter?”
The truth is, telomere shortening is actually a natural process that was meant to be a defense to cancer, which makes sense. If cells could divide forever, wouldn’t that just encourage uncontrollable cell growth and evasion of cell death (the literal definition of cancer)? The point at which cells stop replicating, which is around 40–60 times in humans is known as cellular senescence. This limit is known as the hayflick limit.
This means that life expectancy is actually an inherited trait, seeing as you got your telomere lengths from your parents. However, environmental factors affect telomeres as well. Increased stress is proven to have a correlation with telomere shortening, meaning you literally shave years off your life by being stressed!
After grasping the basics of telomeres it’s also important to understand more about cellular senescence. What exactly are senescent cells?
Senescent Cells
By book, senescent cells are defined as once healthy, normal cells who have either been damaged or their DNA mutated. A bit like zombies really, except they know they have a flaw and stop replicating. Senescent cells send out a signal to the immune system to take them out. However, even though they aren’t dead, and they don’t do anything alive, the signals they send out can actually cause inflammation in other healthy cells nearby. These can cause degrading health issues, among other health problems.
If the immune system responds and sends cells to clean them out, nothing really happens. However, the more common occurrence is that over time, the immune system starts to ignore these signals and stops trying to flush them out, causing lots of further issues.
Again, as we’ve seen before things aren’t the way they seem. Some things might seem good but actually cause the body more harm, while some things may seem bad but do the body more good. In the case of senescent cells, yes they may seem a bit like zombies, but if the body were to respond to every signal and send out fighters to take them out, it could cause the individual to actually heal slower, meaning having senescent cells are actually kind of useful.
Hopefully that clears a lot of confusion up, because it’s time to delve into the more complex areas of cells, proteins and enzymes, and talk about one of the most important aspects of longevity, NAD+.
NAD+
NAD+ is an important molecule that’s responsible for hundreds of reactions that is found in many places throughout a cell. For example, In the nucleus, it helps activate enzymes that regulate and protect our DNA.
NAD+ stands for nicotinamide adenine dinucleotide
While that may seem like a mouthful, just remember that nicotinamide is a form of vitamin B, adenine is just a simple nucleobase (one of the four A, T, C, G pairs), and dinucleotide is a simple compound made up of 2 nucleotides.
All of our DNA is wrapped around histone proteins, similar to how thread is wrapped around a spool. However, when certain sirtuin enzymes are activated by NAD+, it can deacilidate the histone proteins, making the DNA strands coil tighter, altering gene expression. The strands of DNA are very susceptible to damage, and break very often (a daily basis).
An enzyme responsible for fixing this damage is known as PARP1. However, PARP1 (essentially like a repairman) is inactive when bound to the DBC1 (basically his wife) protein. Only when NAD+ binds to PARP1 is DBC1 kicked off and the enzyme is reactivated. This enzyme will then repair any damage done to the DNA strand.
A newborn baby has an extremely high level of NAD+, meaning all the PARP1 enzymes can go around fixing different parts of DNA damage, which is why compared to an old person, a newborn baby heals extremely quickly. A first grader can have a broken arm and be fine in a matter of days, while a broken arm will hinder the elderly for weeks.
However, by the time you’re 20 your NAD+ level will go down 50%. By the time you’re 40 it goes down another 50%. By the time your 60, you only have around 12.5% of the original NAD+ concentration you had when you were born.
NAD+ is literally a biological clock that determines when you will die. Once you get old enough, you won’t have enough NAD+ to activate all your PARP1, making it so you can’t fix the damage done to your DNA on a daily basis. Ever thought about why most people with arthritis have it in their later days? There’s less active enzymes to fix damage done to your cells so more problems are created. This time the solution really is simple. Driving your NAD+ level up can make you heal faster, effectively delaying aging. That’s one way to prolong life. However, there are many more, bringing us to our most well known topic, stem cells.
Stem Cells
When you talk about longevity, most people immediately think about stem cells, and for a good reason. While other cells in your body have a specific purpose, stem cells are undifferentiated, having no specific structures or functions. However, the reason they’re so powerful is that they have the potential to become any other type of cell in your body. The human body uses stem cells to replace worn out cells when they die. For example, your body even replaces the lining of your intestine every 4 days.
There are mainly 3 types of stem cells. Tissue-specific stem cells are found in small numbers throughout most of your body’s tissue, including in the muscle, skin, or liver. These stem cells replace normal cells in their area when they die.
Embryonic stem cells are created from left over embryos that are willingly donated by donors from fertility clinics. Embryonic stem cells are pluripotent, unlike tissue specific stem cells. This means that they can be grown into any type of tissue in the body.
Induced pluripotent stem cells are the third type of stem cells. These were regular skin, fat, or liver cells that scientists changed to behave like embryonic stem cells. Induced pluripotent stem cells also can become any type of cell in the body.
Logically, if humans had more stem cells, more repair could happen, again effectively delaying what we call “aging”, as the process at which our body breaks down can be delayed or even stopped with continued addition of new stem cells or increased production.
Free Radicals and Antioxidants
Antioxidants and free radicals are both naturally occurring chemicals found in your body that are influenced by both diet and environment. In this case, antioxidants are essentially the good guys that block free radicals, who are the bad guys. Free radicals are extremely highly reactive chemicals that can harm other cells. However, like we’ve seen before, they have a purpose with helping liver detoxification, and they also support immune health. However, new research has found a correlation between free radicals’ damage and cancer.
A free radical comes to be when a particle gains or loses an electron. They try to hunt other molecules to take an electron from them to regain their own balance, but this creates a chain reaction of the next molecule doing the same thing, and so on. This is a natural bodily process, and is our way of neutralizing viruses. However, too high free radical levels can damage the very component of what makes up your cells. It’s important to also note that environmental factors help determine free radical concentration. That may all be very well, but what are antioxidants?
Your body naturally creates chemicals called antioxidants, but this naturally created amount isn’t enough to defend against all free radicals, which is many foods supply antioxidants. You often hear PSA’s, ads, and your parents telling you to eat more fruits and vegetables because they are “high in antioxidants”. Most specially cranberries, red grapes, peaches, strawberries and raspberries among others provide your body with the necessity defense to free radicals.
These fruits and vegetables give you the power to prevent or stop the oxidation of other molecules, trapping free radicals. Many things cause free radicals, including obesity, pollution, or overuse of antibiotics.
The oxidative stress caused by free radicals is responsible for all aspects of aging, due to the cellular damage it causes. Knowing this, wouldn’t it be cool to have a way to accurately predict when someone would die?
Epigenetics
Epigenetics is defined as:
The study of how DNA interacts with a multitude of smaller molecules found within cells that can activate and deactivate cells.
To elaborate, genes in DNA are “expressed”, when they are read and transcribed into RNA, which is then translated to proteins through ribosomes. Proteins are what determine much of a cell’s characteristics and function. Epigenetic changes can boost or interfere with the transcription of specific genes. Also, epigenetic changes aren’t affected by cell division, meaning they can carry on for an organism’s whole life. The epigenome, chemical tags attached to the genome of a given cell, can vary in different ways.
Some, such as a methyl group, inhibit gene expression and cause the strands of DNA to coil more tightly. This causes the gene to become inaccessible; it’s still there, but silent.
Other chemical tags unwind the DNA, making it easier to transcribe, which ramps up the production of the given protein. Each of the over 200 different cell types in your body are from the same genome, but have a different epigenome. This could affect your body in a negative way, if for example, an epigenome turned of a gene that fights tumors.
Social experience, diet, and chemicals all around you can affect your epigenomes, which is why identical twins, having the same genome can end up being completely different in both personality and looks. There is a DNA test known as the epigenetic clock that can accurately predict your lifespan based on the methyl concentration in your body. Now that we understand how to measure our predicted lifespan, it brings us to the most burning question of all. How do we actually extend our life?
CRISPR
Science’s secret weapon for treating inherited diseases such as sickle cell anemia or muscular dystrophy lies in none other than CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats. This system guides a protein Cas9, to cut DNA, effectively editing your genes.
So how does this work? Let’s take an example where someone has a faulty DNA in their genome. Firstly, you would have to provide a genetic address for where in the body that faulty DNA is. Cas9 uses that information to find the problem, then cuts it out.
To find the problem, CRISPR uses a guide molecule of RNA that contains a string of over 100 letters, where 20 letters match up with the target area of the DNA. This tells CRISPR exactly where to send Cas9, and it either cuts to delete (where it simply slices off the error parts), or cuts to edit (where it follows a template to cut things out for gene repair).
In a nutshell, that’s science’s most powerful weapon to defend against inherited diseases. Research has shown this can also be put along the same path to defend against age (if that even makes sense), prolonging life.
Hopefully that wrapped up any confusions about longevity, and gave a basic knowledge about the different ways to extend one’s lifespan. Scientists are continuing their work at a progressively and exponentially alarming rate, so any information now can easily be outdated in a couple years. Because of this, research in biology and technology in general is such an interesting field to work on, albeit you have to catch on to new developments quickly. This is a recap of the beginning of my journey through learning longevity, and I hope all of you enjoy learning this as much as I do. Peace!