How Breathing Causes The Worst Disease of All
5 people died a preventable death by the time you finished reading this sentence. It wasn’t diabetes, it wasn’t drugs, it was the one disease no one cares about….
Aging.
Aging isn’t a mystical phenomenon, it’s simple physics. Damage accumulates in your body, and that causes problems — cancer, Alzheimer’s, stroke. These diseases kill people. Lots.
That’s changing.
Presently, 100,000 people die every day because of age related causes- that’s 2/3rds of the world’s total deaths, and 90% of them in the industrialized world. If you live past 40, there’s a 70–80% chance you will die of one of 4 different types of disease:
- Neurodegenerative (ex- Alzheimer’s, Parkinson’s, etc)
- Cerebrovascular (ex- Stroke)
- Cardiovascular (ex- Coronary Heart Disease)
- Cancer
What do all of these diseases have in common?
Breathing causes them. Just kidding, that’s only kind of true, we’ll get to that later. There are two main commonalities:
- They’re not infectious. These diseases build up overtime and come from within us through the accumulation of damage. That’s happening as you read this by the way, enjoy that thought. :)
- We SUCK at fighting them, like I mean seriously suck. Hundreds of billions of dollars are spent annually on Alzheimer’s drugs, yet the treatments might actually be increasing the cognitive decline of patients. Go science!
THE PROBLEM WITH CURRENT MEDICINE
Geriatric care treats these diseases as if they are infections, not as what they really are — consequences of the body deteriorating. Present treatment only serves to combat the symptoms, not the root cause, of these illnesses. The root cause then proceeds to get progressively worse, while the treatment stays the same, not addressing the real issue. Eventually, the body implodes.
SO WHAT IS THE ROOT CAUSE?
The human body experiences 7 different types of damages as summarized by SENS (Strategies for Negligible Cell Senescence).
It is being increasingly more solidified that this is a comprehensive list, and these factors are the only difference between these two:
Let’s explain them.
*Disclaimer: There’s gonna be a lot of sciencey stuff coming up, I’ll try and not bore you to death. HAHAHAHAHAHA get it? Please pay attention, your life depends on it! Oh my goodness I am just killing it with these jokes aren’t I? (Okay I’m done now).
#1: Extracellular Junk
An aggregate of icky proteins that group together outside of cells and have no use other than getting in the way of our cell and tissue function. This clump is normally termed “amyloid,” and the most commonly mentioned example of this is beta amyloid, a plaque found in the brain that has been previously correlated to the presence of Alzheimer’s. However, recent evidence suggests that beta amyloid might not be so bad after all. Another example of extracellular junk is the accumulation of the protein transthyretin found in those with senile cardiac amyloidosis, a major portion of deaths in supercentenarians (people who live past 110).
We aim to solve this problem through one of three methods: “active” vaccines that introduce part of the amyloid into the body in hopes of the cells spurring the immune system to target them, “passive” vaccines that inject external antibodies into the amyloid, and catalytic vaccines in which certain internal human antibodies break down the antigens found in the amyloid into much smaller pieces that are easier for the body to handle.
#2: Intracellular Junk
Certain parts of our cells are damaged overtime, and this “waste” is cleared by organelles (systems) in the cell such as the lysosome. However, the lysosome is not always able to break the waste down, and overtime the lysosome’s function decreases to the point where it stops working and damage runs rampant. This is especially problematic in areas where cells are not replaced, such as in the eyes, heart, and brain.
An example of intracellular junk happens in macrophages, cells that are responsible for protecting our blood vessels from the toxic byproducts of cholesterol. The accumulation of these damaged macrophages combine together to create atherosclerosis, the root cause of heart disease.
Work is currently being done to reintroduce the enzymes that break this garbage down via injection, reversing the intracellular damage. Illnesses such as Gaucher’s disease impair the person from breaking down waste due to the absence of certain genes most of us have, so the presently used treatment for Gaucher’s disease serves a great proof of concept on how we can stop intracellular damage, and as a result, prevent aging.
#3: Extracellular Crosslinks
Most foundational features of our body are created in our youth, reliant on their building blocks, proteins, to maintain their proper structure in order for tissues to sustain a healthy function. Overtime, these proteins react with fluids in the body such as blood sugar and create “crosslinks”: chemical bonds that act like handcuffs by connecting proteins together and impairing their movement.
High blood pressure can be caused by this exact phenomenon. The collagen (connective tissue) in the arterial walls undergoes crosslinking which increases rigidity and causes more blood to be directly carried to organs such as the kidney and the brain at a strong pace. This diminishes the ability of our blood’s filtering structures, which in turn increases the likelihood of having a stroke.
Most of these crosslinks have extremely unusual chemical bonds, and as such there is a high likelihood we would be able to specifically target these molecules. We now know that glucosepane, a very complex molecule, is the largest contributor to collagen crosslinking, and as such is a molecule we can likely fixate on in a variety of different ways. We can use enzymes powered by cellular energy (ATP), use “one shot” self destructing proteins, or even engineer whole pieces of tissues to place into the human body to break these crosslinks.
#4: Cell Loss and Atrophy
Cells undergo continuous damage within the body, forcing them into one of three outcomes: apoptosis (programmed cell death), repair, or senescence (a “zombie” state where cells can no longer divide but are not destroyed). Overtime, this means areas in your body will begin to lose cells, which is combated by your body’s supply of tissue specific stem cells. However, overtime this ability degrades as well, leading to an increasingly jeopardized function of your brain, muscles, and immune system.
One way you can stimulate the growth of your cells is through exercise, but of course that only works to an extent — scientists have two main focuses they are working on right now to solve this problem. Both focuses have the goal of transforming mature cells (such as blood or skin cells) back into patient specific embryonic stem cells (unspecialized cells that can be turned into any cell in the body, and therefore can be used to combat our problem of cell loss) that can be continuously reproduced. These outcomes have immense benefits in contrast to today’s treatment of external organ transplantation because we would no longer be limited by the amount of donors, there would be no fear of rejection of the cells (which is quite common), and everyone would be able to undergo this process indefinitely.
The first method is called Somatic Cell Nuclear Transfer (SCNT), and combines an enucleated (without a nucleus) egg with a somatic (body) cell’s nucleus. This grows an embryo that contains embryonic stem cells we can extract through what is called “therapeutic cloning.” This embryo can also be placed in a surrogate mother to create a clone through a process called “reproductive cloning” (this is actually how the famous Dolly the Sheep was made). Yes, this theoretically means humans can be cloned.
The second method is the conversion of mature cells into induced pluripotent stem cells (a state similar to embryonic stem cells), or the direct reprogramming of these mature cells into the type that is needed (for example, changing supportive heart tissue into heart muscle tissue).
The ability to create new cells and tissues could lead to the creation of entire new organs and indefinitely regenerative bodies! It also serves the potential of playing a key role in curing cancer.
#5: Death-Resistant Cells
Our body is a remarkable organism, but it’s not perfect. The mechanisms of our body work in a way such that some cells become dysfunctional. It’s not a big deal in the short term, but with a couple of decades gone by, this issue gets to the point where there is a severe impairment in bodily function. There are three main subfields within this: senescent cells, fat tissue cells, and immune cells.
As defined in section 4, senescent cells are ones that have stopped dividing as part of the body’s preventative response to danger, such as in potentially cancerous cells. As these cells accumulate, they trigger an inflammatory response, increase the risk of cancer, and interfere with the function of our working tissue.
As we age, two types of cells in our fat tissue begin to behave in abnormal ways that damage our body: Preadipocytes and visceral adipose tissue macrophages (ATMs, but not the ones you like going to). Preadipocytes increase inflammation, insulin resistance, and the amount of unhealthy free fatty acids (which increases the chances of getting heart disease). The amount of visceral (around the liver and gut) fat increases as we age which makes us accumulate ATMs, cells that are also highly inflammatory and increase insulin resistance (this is also what happens in obese people).
The third and final culprit of death resistance is CD8+/killer T-cells, an immune cell whose job is destroying other cells that have been overtaken by illness. Killer T-cells begin unspecialized, but to be able to do their job, they have to specialize in fighting against one illness. The longer we live, the greater quantity and variance of attacking cells we have to deal with in our body, and overtime that forces mass specialization among the killer T-cells. This occurs to the point where the ability to fight certain infections is lost as specific subsets of killer T-cells are crowded out. This explains why as we age we are more likely to die of illnesses that we could have easily dealt with previously, such as the flu or pneumonia, and also why vaccines lose efficacy — there are almost no unspecialized killer T-cells left to train for fighting these diseases.
While these three types of cells are different in their composition and effect, the same general strategy will be applied to solving the problem: killing them. We can get rid of these cells either by creating a drug to target them or having the immune system do so. Both of these methods will likely work by identifying unique molecules on these specific cell types as markers.
#6: Cancerous Cells
There are two different types of damage that negatively impact our genes as we get older, mutations that alter our actual DNA, and epimutations that alter our epigenetics, or expression of our genes. Cancer is caused by a series of both of these that lead to uncontrollable, rapid cell growth. There has been concern that there could be other non-cancerous mutations our genome experiences that are also harmful, however with the research that has been done, and the defences our body needs to have in stopping cancer from occurring at any time, it has been concluded that there likely is no other major concern that isn’t already covered in other types of damages (an example of the end result of these non cancerous mutations includes stopping the function of important cells through the creation of senescent cells, but this issue does not have a solution dealing with the genetics/epigenetics of the cell, but rather with removing and adding cells).
Great, only one monstrous disease to solve here!
One thing that all cancerous cells have in common is their need to reproduce, and an essential component of the cell division process is the maintenance of telomeres. You can think of telomeres as the caps on our shoelaces (DNA), keeping them from wearing out. Overtime, the telomeres wear out, and eventually DNA is removed after each reproduction. At this point, cells begin to lose function. To be able to reproduce as much as cancer does, a successful cancer mutation must have figured out a way to hack one of our two telomere replenishing systems: the enzyme telomerase or the more rare system called the Alternative Lengthening of Telomeres (ALT). If the cancer had not hacked one of these systems, it would have died out before it became life threatening.
SENS has two ideas on how to target this. Firstly, they propose to figure out a way to prohibit cancer’s ability to produce telomerase, however this does not address the issue of ALT and the fact that cancer is infamous for consistent major mutations, and that it’s quite possible that even if we successfully did this, the cancer would figure out how to adapt to deal with it. Secondly, SENS proposes something more radical — removing the genetic functioning of telomerase and ALT entirely so cancer cannot use it. The issue with this approach is that this would of course affect the cells in our body that need these mechanisms, causing essential bodily functions to malfunction much earlier in our lives. In response to this, SENS suggests re-injecting cells into the body every decade.
#7: Mitochondrial Mutations
The mitochondria is the powerhouse of the cell. Thanks high school biology! What my teacher didn’t tell me however, was that this essential cell component can cause some major damage. The mitochondria is very special— it’s in charge of producing energy and it even has its own DNA (mtDNA), but with great responsibility comes great power. In producing energy, the mitochondria also produces waste in the form of substances known as free radicals. This damage has the potential to accumulate into severe problems, such as deleting major parts of the mtDNA. When this happens, these malfunctioning mitochondria create almost no energy but release disproportionate amounts of waste, leading to an increase in oxidative stress.
Free radicals are oxygen reacting with substances in our body, such as oxidized cholesterol, that oxygen comes from our inhalation. This is how breathing contributes to aging. You made it!!!!! *Sorry but not sorry for the clickbait, you’re glad you’re reading this so it’s okay you forgive me ;)*
The way we can go about solving this problem is by either creating a “backup” version of our mtDNA in the nucleus, known as allotropic expression, or by trying to completely move the DNA expression to the nucleus and then move the proteins created into the mitochondria, a process which has largely been happening throughout evolution; we currently have 13 proteins made from our mtDNA, compared to around 1000 a long time ago. What may hinder this solution is the fact that transporting these remaining proteins from the nucleus to the mitochondria may actually be quite difficult because they fold up on themselves, not being able to fit through the pores of the mitochondrial membrane (how the proteins travel). We can try and get around this by analyzing other organisms’ evolution to get ideas on how they shifted to get rid of mtDNA overtime. We can also experiment with ways of slightly altering the mtDNA in a way that it still creates the same proteins in the nucleus, and finally we can try temporarily better “opening up” the transport pathways between the nucleus and mitochondria.
And that’s it, you made it through the hard part! If you’re still here, you’re literally a hero because I definitely would have been gone as soon as I saw my puns.
Please remember, the above list is not even scratching the surface, there is plenty of more research in all of these fields, and so many more I have not even mentioned.
We’ve made huge progress on infectious diseases, but not on those stemming from inside our body until recently. Why? The scientific community largely thought of “living forever” as “woo woo” nonsense until maybe 20 years ago, probably because since our metabolism is so complex, trying to alter factors to produce certain results will always change unexpected things.
Identifying the above damages signifies a major breakthrough — preventing aging is not as complex as we once thought it would be, we can actually conceivably do this! In a few decades it is quite feasible we’ll have a routine damage control check-up and clean all of this damage out of our bodies like we flush our toilets. However that’s still ways off, right now aging is not even recognized by the FDA as a disease, meaning you cannot currently run trials on an anti-aging drug. Progress is being made on this end though.
How are we going to get there?
Mice. Lots of them. Research is going a million different ways, and through progress in all of them we will come up with a comprehensive solution (and make plenty of superhuman animals in the process). I have only outlined one major perspective so far — check out the 95 ways we’ve made mice live longer and the 70 drugs that might make humans live longer.
A different type of epidemic
There is one illness that I have not talked about yet, and one with a major global impact — mental illness. Suicide is in the top 5 leading causes of death from ages 15–49, stemming from a host of issues including depression and anxiety. If we wish to progress as a society, this needs to be taken more seriously.
Road accidents is also up there at the hands of distracted, drunk and fatigued driving, which is another problem we should hope to solve in the next few decades with the emergence of self driving cars.
Misconceptions
A big misconception I formed in doing research on human longevity is that inflammation is the devil and you need to minimize it as much as possible. Inflammation is not actually harmful for you all the time, it is an essential response from your immune system in fighting off infection. What is harmful, however, are the off target effects it causes with the inflammatory response being triggered unnecessarily in what is referred to as chronic inflammation; this is what needs to be mitigated. The lower your inflammation, the worse you are at defending against infectious diseases, but the less likely you are to get diseases like Alzheimer’s. People who have lived to be over 100 likely had a low inflammatory response, avoiding most of the internal diseases, and out of pure luck were not infected. Inflammation is an essential concept to understand as it is tied to practically every disease ever. If you are interested I highly recommend you read more.
One of the damages I talked about was free radicals, which cause oxidative stress. Many people think that you should eat antioxidants until you drop to combat this, but don’t bother — not only would you need to eat like, 120 oranges a day, having too many antioxidants can actually have the opposite effect of our intentions of bettering our bodies, increasing our likelihood of getting diseases. Plus, free radicals are actually beneficial to the body in some ways as well, so even if you could get rid of them all you probably shouldn’t.
Only our body makes things that are simultaneously good and bad, and we find treatments that make us both better and worse. This essentially summarizes my experiences researching aging.
If you want more information the topic of antioxidants and free radicals, click here.
Okay Rikard, what will actually make me live longer/better?
“Sleep is for the weak, I only need 3 hours.” The percentage of people in the world who that applies to rounds to 0, so trust me, it’s not you. You need at least 7 hours of sleep. If you want to get your mind blown on the importance of sleep, watch this podcast. It should be mandatory global viewing.
Exercise literally makes you smarter. BDNF (Brain Derived Neurotrophic Factor), the hormone that enables your brain’s neurons to connect with one another (neuroplasticity) and promotes the growth of new neurons, increases substantially working out a bit everyday. And I mean, exercise is the most effective drug there is for everything from sleep to stress. If you could put the benefits of exercise into a pill you’d be taking 100 a day. 10 out of the 1 million benefits are summarized here.
Diet? I hope you don’t need convincing on this one. Fast food addiction slowly turns people into an unrecorded documentary of Super Size Me.
If you have all of those down pat, you could look into optimizing your microbiome, the ecosystem of bacteria living in your body that seems to be the secret driver behind our well-being in an enormous amount of ways we are only now beginning to understand. 90% of our serotonin, the hormone that regulates our mood, is found in the microbiome. Happy bacteria, happy you. Check out more information on it here.
Caloric restriction and intermittent fasting also seem to be extremely beneficial for a host of reasons in the human body, such as stimulating autophagy which could decrease the risk of cancer. Their effects on actually increasing life span may be negligible on humans because we already live so long, however it remains to be seen.
There are 3 pathways that seem to be heavily associated with aging, mTOR, AMPK and Sirtuins, so any drugs that could positively affect these pathways could be a promising idea (note the word promising, please do your own research, some of these drugs are not yet validated enough for human consumption). You want to decrease the use of your mTOR pathway, and Rapamycin, an immunosuppressant transplant patients use, does exactly that; it has been insanely successful in increasing the lifespan of dogs, and currently there is much research trying to get around rapamycin’s negative side effects to make it publicly usable. Unfortunately, eating lots of protein and consuming amino acids (like BCAAs for working out) seems to decrease your lifespan by activating this pathway.
The AMPK pathway, our body’s way of fighting against obesity and diabetes, weakens overtime, and metformin, a drug used for diabetes patients, seems to combat this. Metformin is currently undergoing a trial in attempts to pave its way to FDA approval after incredibly promising results.
Finally, there are drugs that stimulate the sirtuins pathway, certain genes that protect humans from deterioration and disease. We can stimulate our pathways by increasing our NAD+, an essential molecule that we lose half of by the time we turn 50. We can solve this by taking substances such as NR, NMN, and Resveratrol.
To fight against oxidation, you should make sure to ingest a healthy amount of antioxidant foods, however don’t go too crazy (as mentioned in the last section).
Basically, follow all the advice your grandmother gave you: eat healthy, sleep, workout, and take immunosuppressant and diabetic drugs.
But Rikard, isn’t aging natural?
Glad you asked. All “human longevity” treatment is doing is treating damage/sickness as we have done for forever, it is just doing so more effectively. These research scientists are not in the business of “curing death,” they’re in the business of curing cancer, Alzheimer’s, heart disease, and more. This is just as natural as treating cancer with chemotherapy, using antibiotics for an infection, or vaccinating to prevent against Polio. What we currently do is wait until when we are diagnosed with a disease, and desperately use most of our health system’s resources to try and fix the problem, while all we are doing is prolonging the misery while we continue to break down. We spend almost 50% of our healthcare resources on patients in the last few years of life where they are miserable and barely alive, that’s trillions of dollars annually. Not only will human longevity science better the quality of everyone’s lives, it will save unimaginable amounts of money that can be put towards the greater good.
But Rikard, what about overpopulation?
You’re starting to sound a little naggy, but I’ll bite. This population problem is largely overblown — as the quality of life increases the reproduction rate decreases, and it is quite likely we will teeter off around 11–12 billion and earth will be perfectly sustainable. Don’t believe me? Take a look at the data. Of course, everything right now is anyone’s best guess, we can’t know for sure. However, based on the information we currently have, it is definitely plausible that working on human longevity will be a massive net positive to society. In the event it isn’t, future humanity should have the ability to make that choice — they will have far more information than us, and we can’t possibly assume we know enough now to decide it is worth not working on this.
RIKARD WHAT ABOUT LACK OF ACCESS?!
OKAY NOW YOU’RE ANNOYING ME. If you have any arguments whatsoever against human longevity research, it is likely discussed on this webpage.
So What?
Human Longevity is the most important problem we can solve because it affects us all. On top of that, it’s super cool.
The amount of money and interest in this space is sparingly low, so if you are interested, dive in! I really hope this article has helped at least one person change their perceptions about aging and has encouraged them to learn more. Be sure to follow me to tuned in for more!
Disclaimer: I am not a medical professional, I simply hope to inform and summarize what I have learned. Please do your own research and come to your own conclusions.
