Do you remember the first time you woke up on a wet, cold, rainy day and your joints ached?
What about the first time your knees talked to you climbing the stairs?
Was your reaction the same as mine? A horrified whisper of so it begins followed by a violently dramatic shout of whyyyyyyy that made your significant other cry with laughter? No? That was just me?
Well, alright, perhaps the details of your reaction were a bit different. The general sentiment behind it was pretty similar to what I experienced, though, right? An odd mixture out of a sense of inevitability, begrudging acceptance, the kind of mild dread that comes along with drives to the dentist, and a nagging sensation of: why? Why do I have to get older? Why does my body have to age?
Now, neither you nor I meant that question literally when we asked it in our moment of despair. It was more just an expression of frustration at the seemingly inevitable.
Other people, though, do ask that question literally. Why does the human body age?
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Aging is clearly a real, physical thing. Young bodies both look and function differently than older bodies. Something has to be different between the two. What is it? Where does it come from and why?
The people asking these questions literally, aging science researchers, have put a lot of work into trying to find answers. Though not every mystery has been solved, they have made great progress towards helping us understand both the why and how of human aging.
This is exciting news not just because it is finally slaking our inborn curiosity about aging, but also because aging knowledge is aging power. It is the ultimate tool for life-long wellness! The more you know about aging, the more effectively you can make decisions about how to protect your health, long-term.
Why Do We Age?
So, why do we age?
Well, based on the current research, there are two answers to that question: the short answer and the several-billion-year-long answer.
I think we’d better stick to the short one for now!
The simplest, shortest answer for why humans age is: over time, the cells of our body stop being able to do their jobs.
At first glance, that probably doesn’t seem like rocket science, but in a lot of ways, it’s a game-changer for how we think about aging. Everyone knows aging is a natural process. All living beings (we know of) grow up, age, and then die. For a long time, it seemed reasonable to think aging might be the inevitable, ultimate destiny of cells — something cells were designed to do, even though it’s destructive for our health. It was suspected that a cell is born with programming that forces it to ultimately age, not so different to how lighting the fuse of a bomb ultimately forces the bomb to explode.
Discovering, instead, that aging is really just malfunctioning cells throughout the body changes the whole dynamic. It means that aging is not programmed into your cells.
Why is that a big deal?
If aging is not programmed into your cells, that means that not-aging is actually your default setting. In other words, your body doesn’t actually want to age, but something is making it. Something messes up how your cells work, and then you age.
Do researchers have any candidates for what’s responsible for messing up how your cells work when you age?
Yes. Two of them.
- Unhealthy DNA
- Unhealthy Proteins
Typically, when you think of unhealthy DNA, you think of genetic disorders — diseases caused by inheriting unhealthy DNA from your parents. That DNA, the DNA that causes genetic disorders, is in your DNA from birth. That’s not the kind of unhealthy DNA involved in aging, though. (At least not usually).
The type of unhealthy DNA that causes aging is DNA that was healthy when you were born but became unhealthy later.
How can some of the healthy DNA in your body you inherited from your parents just become unhealthy?
Mistakes and Mutagens: Making DNA Unhealthy
It turns out there are actually all kinds of things that can just randomly, sometimes completely accidentally, make healthy DNA unhealthy.
One of the most common ways healthy DNA can be made unhealthy is by mistakes when your cells divide. Every time one of your cells divides into two cells (which is how you grow, heal wounds and replace dying cells), all of your DNA — the entire 2 meters of it — has to be copied perfectly. That’s billions and billions of DNA bases that have to be put together in the absolute perfect order, and sometimes, your cell makes a mistake.
The other common way healthy DNA becomes unhealthy, is by coming into contact with mutagens. Mutagens make your DNA unhealthy by either breaking the strands apart or causing them to bind together in weird ways they shouldn’t. Both of these are very unhealthy for your DNA.
Figure 1: How mutagens damage your DNA
Where do you run into mutagens?
All over the place.
They are found in everything from cigarette smoke and air pollution to food, everyday things you buy from the store, and just plain-ol’ sunlight! Not to mention that your body actually provides you with your own personal, constant supply of a special kind of mutagen, called reactive oxygen species, by breaking down food for energy. Your DNA is always being bombarded with things trying to make it unhealthy.
Why does unhealthy DNA caused by mutagens or mistakes make you age, but unhealthy DNA you’re born with doesn’t?
Your body tries to fix unhealthy DNA you were not born with.
Fixing DNA and Aging
Unlike inherited unhealthy DNA, unhealthy DNA created by mutagens or mistakes has something to compare itself to (the old, healthy DNA that’d been in your body for years). The first time it tries to do its job after it’s changed, it says: “Hey, wait a second! I look funny! That’s not where my cytosine was last week! Something’s up!”
Figure 2: Is this really a typo?
If the only way you’d ever seen the alphabet written was right here, you’d never know the order was wrong! Neither can your DNA know inherited mutations in its sequence are “wrong” and need to be fixed.
When this happens, the DNA signals a group of proteins called DNA repair enzymes to come over and give it a check-up. DNA repair enzymes act like DNA-doctors. They examine the DNA that asked for a check-up, diagnose what’s different than in healthy DNA, and then (try to) fix it.
Most of the time, the DNA repair enzymes do a great job — they find the problem and fix it. Sometimes, though, there are other outcomes. And here’s where unhealthy DNA starts to be able to mess up how your cells function and cause you to age.
The DNA Can’t Be Fixed
Sometimes, the DNA repair enzymes find the problem, but it is too difficult to repair. They let the DNA know that it can’t be fixed. Then the DNA makes one of two choices: commit suicide or enter a holding pattern.
If the problem is really bad, and the damaged DNA can’t do its job to keep the cell alive, it usually opts to commit suicide.
This is a kind gesture by the DNA. It knows that if it removes itself from your body another cell with healthy DNA that can do its job will replace it. That keeps you, as a whole person, healthy, even though the cell itself dies.
If the problem is medium bad, the DNA usually decides to put the cell into a kind of holding pattern called senescence. It keeps the cell alive and doing its job, but nothing else. It doesn’t really grow anymore. It doesn’t divide to make new cells, either. And, if more DNA becomes unhealthy, the DNA will force the cell to opt for suicide, rather than trying to fix itself. Basically, the DNA forces the cell to take on an “I’m a goner, so let me help you as much as I can before I go” mentality.
This is another kind gesture by the DNA. If it’s healthy enough to keep you healthy, it does so, but it makes sure not to grow or divide, so as not to pass on its unhealthy DNA to any other cells. It lets its spot be taken over by a different, fully healthy cell, instead. That keeps you healthier in the long run, even though it means the cell itself will, ultimately, die.
While the cell’s intentions are kind when it enters senescence, its decision causes you to age.
What did we say causes aging again? Right — a breakdown of normal cell function! A cell in senescence, by definition, cannot do everything a healthy cell can. It can’t grow and it can’t divide, two very important normal cell jobs.
The DNA Repair Enzymes Can’t Find The Problem
The second outcome of a DNA check-up that can lead to aging is a false negative (or all-clear) from DNA repair enzymes. Sometimes, despite their best efforts, DNA repair enzymes don’t catch what’s wrong with the DNA. They let the DNA go, without fixing it or sending up red flags that it can’t be fixed. They just send it on its way.
This is perhaps the worst possible outcome for your health and for aging. Unlike cells that commit suicide or go into senescence, cells with unhealthy DNA given an all-clear, just keep going about their business like normal, but with unhealthy DNA.
The cell grows. It divides. It passes on damaged DNA to other cells.
And the cell uses its unhealthy DNA to make: unhealthy proteins.
Which brings us to our next topic.
Proteins often get boxed-in to their role of helping your muscles function properly, but proteins have many, many more jobs in the body than just letting you do a push-up! In fact, proteins are responsible for a ton of jobs in each of your body’s cells.
- help build all cell structures
- breakdown and recycle damaged cell structures
- chop up and burn food for fuel
- package extra food for storage
- carry molecules and building blocks between parts of the cell
- transport messages between areas of the cell
- coordinate cell growth
- synchronize cell division
- carry out cell suicide
- protect healthy DNA
- repair unhealthy DNA
- tell your DNA when to turn on or turn off a gene*
*A gene is a section of your DNA that tells your cell how to make one specific protein. If you think of your DNA as a book of instructions on how to make a you, a gene is a single sentence.
In addition to all these super important jobs within each cell, proteins are also responsible for carrying signals between cells (not to be confused with carrying signals between different parts of the same cell). When proteins carry signals between cells, they serve as extremely important messengers. They let cells know when their neighbor needs help, when the organ a cell is a part of is in danger, and when there is an infection all the way on the other side of the body. Proteins let your body function as one unit, not as billions of single cells sitting around in one spot!
I think you can imagine how having unhealthy proteins — proteins that can’t do their jobs — can keep cells from functioning normally. Proteins are responsible for basically every function of a cell! If they aren’t working correctly, of course, your cells aren’t either.
But it’s even a little worse than it seems at first. Proteins are actually so in charge of everything, that they are responsible for keeping proteins healthy. That means that having unhealthy proteins in your cells, depending on which proteins they are, can make it so fewer and fewer of your proteins work. And then you are in one heck of a mess.
Proteins Keeping Proteins Healthy: The Proteasome and Autophagy
There are two key types of proteins responsible for keeping other proteins healthy. These are the proteins that make up something called proteasome and the proteins responsible for helping your cell carry out a process called autophagy.
The proteasome is a giant complex of proteins that you find in each cell. It’s kind of funny looking — like a slinky!
Figure 3: Structure of a Proteasome
Unlike a slinky, which serves no worldly purpose except to freak cats out, the proteasome is essential to keeping your cells healthy.
The proteasome systematically chops up broken or malfunctioning proteins. When a protein enters a proteasome (through the center — like entering a tunnel), it is broken all the way down to amino acids (the smallest building block of a protein) so the cell can reuse them and build new, healthy, functioning proteins again.
If your proteasomes stop working, become damaged, or are unhealthy, broken proteins stay in your cells. These unhealthy proteins can’t do their jobs in your cell and that is a situation that can spiral out of control pretty quickly.
Let’s look at a couple of examples to help explain why.
Let’s say there’s a build-up of reactive oxygen species (those mutagens I mentioned above) in your cell. It damages your DNA right in the gene that encodes for one of the proteasome proteins, and that damage sneaks past your DNA repair enzymes. Now, your proteasome protein isn’t being made the right way anymore. It stops breaking down broken copies of a protein called glutathione synthase. Glutathione synthase is responsible for making a molecule called glutathione, which soaks up reactive oxygen species like a sponge, keeping them from damaging your DNA.
Uh-oh. Now there is less glutathione and, therefore, even more reactive oxygen species. Those reactive oxygen species that didn’t get soaked up can now damage other parts of your DNA. As more and more of your DNA gets damaged, your cell gets more and more sick and functions less and less well.
Or how about this example.
Imagine your proteasome was damaged by a reactive oxygen species directly (yeah, they can do that — sneaky little buggers). Now your proteasome isn’t working very well. It stops breaking down a protein carrying a message to your cell from its neighbor: “Hey! We’ve got an injury over here! We need you to divide and heal the wound!”
Your cell divides. And divides. And then it’s dividing so fast that it starts making mistakes when trying to copy your DNA. Now your DNA gets a mistake in it right where the gene responsible for stopping your cell from dividing is stored.
Your cell can’t stop dividing anymore. It grows totally out of control, a situation you know as cancer.
These situations might seem a bit far-fetched. Really? Unhealthy DNA right at the spot that should stop the cell from dividing? Yeah. It’s super unlikely. The problem is, you have so many cells that, even though these things are really unlikely, they still happen, once in a great while. And that is enough.
The principle behind autophagy is very similar to that of the proteasome. Rather than only being able to break down proteins, though, autophagy is able to chop up whole cell structures.
In autophagy, broken or malfunctioning cells structures, such as giant protein complexes (like a proteasome) or organelles (like mitochondria) are broken down and recycled. To do this, proteins, called ubiquitin, drag the broken structure to something called an autophagosome. This is like a mini stomach right in the middle of your cell. It is full of strong acid and digestive enzymes that can break the broken whole structure down into its smallest parts, just like your stomach does with the food you eat.
Autophagy is just as important for keeping your cells functioning properly as the proteasome. Especially since autophagy lets you get rid of broken mitochondria. Mitochondria are the organelles in your cell that are responsible for burning food for energy. They are where reactive oxygen species are made. And when mitochondria are broken, they make way, way more reactive oxygen species.
That, of course, puts your whole cell at risk: your DNA, your proteins — everything!
What Happens to Your Organs When You Age?
Okay, so we’ve been through how changes in your DNA and your proteins make individual cells not work, but how does that lead to changes in your organs and your whole body — the parts of aging you see and feel every day?
Well, similarly to how each of your cells needs healthy DNA and proteins to function properly, each of your organs needs healthy cells to do their jobs.
Each of your organs is, of course, made up of millions and millions of cells which have to work together for the organ to be able to work. Having one or two of the cells not working perfectly, doesn’t make that much of a difference. At some point though, if too many of the cells aren’t working or are in senescence and can’t help replace cells that died, the function of the whole organ suffers.
Aging and the Organs
The symptoms you feel in your body when your organ(s) stop working properly depend entirely on what the healthy function of the organ should be. A super general comparison of healthy organ and aged organ function is summarized in Table 1 (click on the organ name to learn more).
Table 1: Effects of aging on Each Organ
Is supposed to:
But when you age it/they:
Be a solid, resilient barrier to the outside world
Becomes thin, fragile and has difficulty healing, causing it to scar
Keep your body moving and support your bones and organs
Becomes weak and unstable
Process light and send messages to your brain so you can visualize the world around you
Let less light through and have trouble converting light to nerve signals, making it hard for you to see
Process data, control your organs, hormones, movements, thoughts, store memories and help you communicate
Does poorly at all of these tasks, causing changes in thinking, memory, hormones and overall health
Keep dangerous bacteria and viruses out of your body, kill cancer cells and leave the rest of your healthy cells alone
Has difficulty telling dangerous and non-dangerous signals apart, so infections are fought off slower and autoimmune attacks increase
Pump blood and oxygen to your whole body
Has trouble pumping with normal, healthy force
Let blood flow to your whole body and regulate your blood pressure
Don‘t expand and contract as they should, causing high/low blood pressure and changes in blood flow
Detoxify your body, regulate your metabolism
Has difficulty detoxifying your body properly, can‘t regulate your metabolism properly, leading to too much fat and/or sugar in your blood
Preventing Aging: From Theoretical Knowledge to Practical Tools for Life-Long Wellness
Recognizing that all the complicated symptoms of aging — from skin wrinkles to cancer — basically all boil down to the fact that your cells just aren’t working properly begs the question: can we stop it?
If you could keep your DNA from becoming unhealthy and prevent your proteins from becoming unhealthy, could you keep the aging process from happening?
Researchers admit that there is theoretically no reason that we couldn’t. Practically, though, it looks looks like coming up with effective, practical tools for life-long wellness that stop aging where it starts is pretty impossible.
The main reason for this is: statistics. We have so many cells and, as we discussed above, mutagens are everywhere. We cannot protect all of our cells, all of the time, from all of them. Especially since we have to make our own mutagens to live!
Based on the number of mutagens we come into contact with and the number of cells we have, scientists now think that, just based on a pure statistics, humans can’t really live longer than between about 115 and 125 years. Let’s split the difference and call it about 120 years.
This actually is remarkably close to the oldest ages people have actually been found to live to, with the absolute oldest ever recorded being 122 years.
While in some ways that is discouraging news (we do likely have to age, after all), there is a serious silver lining to this cloud. 120 years is much, much longer than the current life expectancies for most people around the world!
As of 2015, the average life expectancy worldwide was just 71.4 years: around 74 for women and 70 for men. Of course, those numbers include very poor countries like Burundi (life expectancy: 55) and active war zones like Syria (life expectancy: 61).
If you look at higher income areas, like Europe or North America, the numbers are a bit higher than the world average (78 and 77, respectively), but not by that much and not for everyone in those countries. In very poor areas within the United States, for example, the average life expectancy is down near that of Syria — in the 60s!
(Curious about your personal life expectancy? Check out this cool calculator.)
Regardless of where you look, though, life expectancy is nowhere near 120. Even taking the numbers for the most well-off countries, like Norway or the Netherlands, you’re still a full 40 years short of how long scientists think we can live.
40 years is a long time. That’s a ton of extra vacations. A ton of extra time playing with grandkids! Heck, 40 extra years means meeting a ton more grandkids — we’re talking possibly up to your great-great-great grandkids!
Is there anything we can do to tweak how we age to add (at least some of) those 40 extra years to our life? And is there any way to make sure those extra years are healthy years?
Those are the questions we’re going to tackle next time!
So stay tuned for Ways to Live Longer and Healthier: An Expert’s Guide!
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