by Dave Asprey
MITOCHONDRIA AND THE FOUR KILLERS
As I fought my way back from experiencing the many symptoms of aging, my likelihood of dying from the Four Killers dropped dramatically. That’s because—surprise, surprise—they all have one underlying issue in common: the cumulative damage to your cells, and in particular, to your mitochondria, that takes place over the course of a lifetime. This damage occurs in all of us, though at varying rates. Some damage stems from the bad choices we make, but much of it is simply the price we pay for the basic functions that support life—like metabolizing food and breathing.
You die a little bit every day from these cuts that make you weaker in the short term and hasten your decline in the long term. Staying alive requires avoiding as many of those cuts as possible, but they are all around you—in your food, your air, your light sources, and throughout your environment. You may not associate these cuts with your likelihood of aging prematurely or of developing a degenerative disease, but like every other aspect of your biology, they are all connected. The cuts lead to aging, aging leads to disease, and disease leads to death.
If you’re in your twenties or thirties, you may think you’re in the clear—that these cumulative cuts aren’t affecting you yet. But the cuts from bad choices or a toxic environment begin to add up from an early age—and they’re hurting you even if you’re not currently feeling their effects (such as weight gain, brain fog, muffin top, and fatigue). And it’s a lot easier to avoid damage to your mitochondria than it is to reverse it later.
Your mitochondria are responsible for extracting energy from the food you eat, and then combining it with oxygen to produce a chemical called adenosine triphosphate (ATP), which stores the energy your cells need to function. When your mitochondria conduct this process efficiently, they produce lots of energy so you can perform at your greatest potential—like a young person. But if your mitochondria become damaged or dysfunctional as you age, they begin producing an excess of free radicals in the process, which leak into the surrounding cells and lay the groundwork for the Four Killers. Congratulations, you are now old.
Even young, efficient mitochondria produce some free radicals as by-products of creating ATP, but they also make antioxidants, compounds that inhibit the damaging effects of free radicals. This is why products containing antioxidants have “anti-aging” properties. While popping antioxidant supplements and using skin-care products containing antioxidant-rich ingredients are worthwhile interventions, they are, frankly, the low-hanging fruit of our Super Human tree. For you to truly remain young, those antioxidants have to be produced by your body—your mitochondria must create at least as many of them as it does free radicals. When your mitochondria become inefficient, they make an excess of free radicals and fewer antioxidants. And you can’t slather enough serums onto your skin to fully counteract the damage created by this imbalance.
Your mitochondria are also in charge of triggering cellular apoptosis, programmed cell death that occurs when a cell is old and/or dysfunctional. If your mitochondria are sluggish, they may not trigger apoptosis at the right times, which can result in healthy cells dying off before they should or dysfunctional cells sticking around past their prime and aging you before your time.
When you’re still young and exploding with mitochondrial energy, you can take some of these hits. You can eat garbage, drink too much cheap beer, forgo sleep, and still function pretty well because you’re producing lots of antioxidants and energy. As you get older, you start to see that you can’t stay out all night drinking and still really bring it at work the next day. By the time you wake up to this new reality, you’ve already taken a lot of hits that will age you in the long run. But you’re likely to keep running at the edge of what you can perceive, so the damage stacks up without you even knowing it.
Well, what if you made better choices throughout your life so you took fewer hits over the course of decades? Then when you got to the age of seventy you might look and feel more like fifty because you simply suffered less damage. You’re never going to be able to avoid all the cuts—again, simply breathing creates some amount of wear and tear over time. It’s a matter of preventing as much damage as possible, which happens to dovetail nicely with the first rule of biohacking: Remove the things that make you weak. This is in and of itself a powerful anti-aging strategy.
When your mitochondria start to slow down and create an excess of free radicals, the result is widespread chronic inflammation throughout your body. Inflammation is such a hot topic in the field of longevity that you probably already know how closely it’s linked to aging. When I was sick and old as a young man, I knew I was inflamed, but I had no clue this stemmed from mitochondrial dysfunction, nor did I know that inflammation was more than a painful annoyance. I had no idea that inflammation creates the ideal circumstances for each of the Four Killers to thrive.
HEART DISEASE
A condition known as atherosclerosis, hardening of the arteries, is the first obvious clinical sign that heart disease has started. But what causes this? A thin layer of cells called the endothelium lines your arteries. When the endothelium is damaged, fats can cross into the arterial wall and form plaques. This is bad enough, but when your immune system picks up on the fact that this is happening, it creates chemical messengers called inflammatory cytokines to attract white blood cells to those plaques. This is an inflammatory immune response. When those plaques rupture because they are so inflamed, blood clots form, and these clots are the real cause of most heart attacks and strokes.
While some doctors are hesitant to definitively state that inflammation causes heart disease, it’s hard to refute the evidence that inflammation is a big step in the disease’s process, and most functional medicine practitioners now identify inflammation as a bigger health risk than cholesterol levels. In a landmark study conducted by researchers at Brigham and Women’s Hospital that followed ten thousand participants for twenty-five years, the data revealed that participants who reduced their inflammation levels also significantly lowered their risk of cardiovascular disease and the need for heart surgery without any other medical interventions.5
A new study out of the University of Colorado at Boulder shows that your gut bacteria actually play a role in the inflammation behind atherosclerosis.6 As animals (and likely humans) age, changes to gut bacteria harm the vascular system and make arteries stiffer. That stiffening came from inflammation. The gut bacteria of older mice actually produced three times the normal amount of an inflammatory compound called trimethylamine N-oxide (TMAO). When researchers used antibiotics to knock out the old mice’s gut bacteria, their vascular systems magically returned to those of young mice. The researchers concluded, “The fountain of youth may actually lie in the gut.” After following the lifestyle recommendations in this book, I am happy to report that my last test showed that I had zero species of gut bacteria that produce this harmful compound!
Even more mind-blowing, a 2017 study out of the University of Connecticut in Storrs revealed that the fat molecules that form plaques in your arteries come not from the fat in the food you eat, but directly from bad gut bacteria.7 This turns everything that conventional doctors tell us about dietary cholesterol on its head and means you have permission to laugh when people repeat the myth that a “plant-based” diet is better because it doesn’t contain saturated fats like butter that will somehow “stick to” your arteries. It also shows the importance of healthy gut bacteria and mitochondria for a long and energetic life. (More on this in chapter 11.)
We know that the mitochondria in our cells, which themselves evolved from bacteria, communicate with the bacteria in our gut. Bacteria communicate with one another via chemicals (like hormones), light, or physical movement. They even gather around and trade bits of their genetic code in a microscopic swap meet for bacteria superpowers. This is called a plasmid level exchange. Imagine a group of Marvel superheroes hanging out at headquarters. Wolverine says to Spider-Man, “Do you want my ability to grow claws? I’ll tra
de you for your super speed.” This happens constantly in our guts and in the world around us, which is why drug-resistant bacteria spread so rapidly. It’s also why we must end industrial livestock practices that require antibiotics. The bad bacteria that evolve in that environment find their way into your gut and make it hard for you to live well for a long time.
So there is clearly an inflammatory and gut bacterial connection to heart disease. Plus, we know that when you have the right kind of bacteria in your gut they can actually transform the foods you eat into short-chain fatty acids, which are highly anti-inflammatory. Nurturing healthy gut bacteria is one of the most important things you can do to become Super Human, and you’ll learn how later.
Look, I remember what it felt like when my doctor, complete with white lab coat, looked right at me and said in a matter-of-fact voice, “You are at a high risk for heart attack and stroke.” I recall the bewilderment and fear in my gut as I stared my own mortality in the face. That happened when I was still in my twenties, and thanks to the information in this book, it is not an issue for me anymore. But even when I was just a kid, I had symptoms of cardiovascular issues, specifically blood pressure instability, a condition normally reserved for much older people. When I stood up quickly, my blood pressure was too low to keep oxygen in my brain. This caused me to start seeing stars and feel extremely fatigued. As a youngster, I would lean my head forward after getting out of a car in order to avoid seeing stars. I was so used to this that I thought it was how everybody lived.
Now I know these were symptoms of postural orthostatic tachycardia syndrome, or POTS, which is often triggered by toxic mold exposure but can also happen with age. In either case, inflammation disrupts the line of communication between the nervous system and the endocrine (hormonal) system. The disruption of these signals leads to fatigue and blood pressure instability, and can lead to symptoms of attention deficit disorder (ADD)8 and Asperger’s syndrome,9 which I certainly exhibited as well.
This manifested in my not knowing the names of most of the kids in my class, even at the end of the school year. I had zero facial recognition and no understanding of basic social skills. My body was filtering out those signals to conserve energy because my biology was so trashed. Our bodies will always prioritize survival over socialization, and I didn’t have enough energy to go around.
It may be hard to comprehend how cognitive symptoms could be connected to vascular issues, but as you will learn in this book, everything in the body is connected. And that includes the diseases that age us and too often lead to premature death.
DIABETES
While the idea of inflammation “causing” heart disease remains controversial, we have definitive proof that type 2 diabetes is an inflammatory disease,10 and having diabetes dramatically increases your risk of cardiovascular issues. More than ten years ago, researchers discovered that when macrophages—immature white blood cells that play a key role in the immune response—find their way into otherwise healthy tissues, they release inflammatory substances called cytokines that cause nearby cells to become insulin resistant.11
In insulin resistance, the body has an impaired response to insulin, which is normally responsible for moving sugar out of the blood and into your cells. The result is that your blood sugar levels are not well regulated and become chronically high. Because chronic high blood sugar will eventually lead to diabetes—a disease in which the pancreas is unable to produce enough insulin to keep up with the body’s demands—a diagnosis of insulin resistance is most often accompanied by the label prediabetic. Prediabetes is so common now that it almost seems like no big deal. The CDC says that more than one out of every three Americans is prediabetic. But it is actually a huge deal because having diabetes dramatically increases your risk of developing the other killers.
Excess blood sugar causes damage to the entire vasculature, so if you have diabetes, you’re more likely to have heart disease or a stroke. High blood sugar also causes dangerous nerve damage by injuring the walls of the capillaries that bring blood and nutrients to your nerves. This is called peripheral artery disease, and it is especially common in the legs and feet, which is why you may have heard of people suffering from diabetes needing foot or leg amputations. When this happens in the eyes, it causes blindness. If that’s not bad enough, diabetes can damage your kidneys’ filtering system, resulting in kidney disease. And finally, the higher your blood sugar, the greater your risk for Alzheimer’s disease, to the point that some researchers call Alzheimer’s “type 3 diabetes.” So you’ve got to keep your blood sugar levels stable, no matter what.
You may think you’re off the hook if you are not overweight, but you can be thin and still be prediabetic (or even fully diabetic). Those problematic macrophages are most likely to trigger inflammation in adipose tissue, aka fat. So the more excess fat you’re carrying, the higher your chance of becoming insulin resistant and developing type 2 diabetes. But the same thing can happen if you are not overweight but have excess visceral fat, which is the type of fat that’s packed around your internal organs instead of underneath the skin. This “skinny fat” is even more dangerous than fat you can see.
There is new evidence that maintaining normal amounts of muscle strength as you age can help ward off this killer. In a study following five thousand people for over twenty-five years, participants were given regular strength tests. The risk of diabetes was slashed by 32 percent in those with even moderate muscle strength as opposed to those with low muscle strength.12 The reduced risk did not change if the participants were even stronger, so you don’t have to get ripped to live longer, but you should avoid carrying excess fat.
I had no idea as an obese teenager that inflammation was making it difficult for me to control my blood sugar. Instead, I bought into the myth that I just wasn’t trying hard enough to lose weight. I exercised a ton and constantly watched what I ate. For breakfast, I had Grape-Nuts, which were supposed to give me energy, and skim milk, which was meant to do my body good. But they did neither of those things. I distinctly remember one morning in ninth grade eating a bowl of Grape-Nuts with skim milk to prepare for a big soccer match. I was convinced this was a healthy breakfast, but I didn’t perform very well in the game. I thought to myself afterward, Well, that didn’t work the way it was supposed to.
This was the first time I questioned conventional wisdom about what was actually good for me. It would be many more years before I started to get real answers, but in my desperation I started experimenting with things that no teenager should need to explore. I was sick of feeling like an old man. So I started reading everything I could get my hands on that offered some advice for how to feel and perform better. While my peers were (I assume) out drinking and having fun, I was at home biohacking.
For my knee pain, I tried the glucosamine pills from the health food store, and they brought some serious relief. I didn’t know it then, but glucosamine inhibits glycolysis, your body’s breakdown of glucose (sugar). As a result, your body has to get energy from fat instead of sugar, which helps prevent insulin resistance. Recent research on mice has found that glucosamine promotes mitochondrial biogenesis (the birth of new mitochondria) and mimics the effects of calorie restriction.13 And there are plenty of studies to show that calorie restriction (a diet consisting of fewer than 1,200 calories a day) in conjunction with good nutrition extends life-span. In mice, calorie restriction can extend life-span by as much as 40 percent. Most researchers estimate that the impact on humans is more like 10 percent, which is still pretty amazing14—if you’re willing to be hungry, anyway.
If you’re like most people, you don’t enjoy feeling hungry, and you don’t want to restrict your calories to fewer than 1,200 a day. The good news is that researchers have been testing compounds that mimic the benefits of calorie restriction without the starvation. Glucosamine is one of those compounds. In one study, glucosamine extended the life-span of mice by 10 percent.15 And it most likely helped with my knee pain because of the way it impac
ted my body’s sugar metabolism.
Despite this small win, I was heavier than ever and fed up. In college I spent eighteen months working out six days a week for an hour and a half at a time while on a low-calorie, low-fat semi-vegetarian diet with lots of rice and beans and everything that was supposed to be good for me. I got really strong, but I was still covered in blubber, and later blood tests revealed that I was prediabetic thanks to all that fat and the inflammation it was fueling.
I knew something had to change, but I had no idea what that thing was. Then one day while I was at a coffee shop getting my daily fix, I spotted a weightlifting magazine on a rack. No one I knew in my small farming town read weightlifting magazines, but something on the cover caught my eye. It said, “How to grow abs!” Looking down at what I had grown—which you could more accurately call flabs—I thought, I have to read this. The goal seemed impossible in the world I lived in.
As I sipped a triple latte, I read an article by a body builder with impressive abs who said that sugar and carbohydrates make you fat. That advice was radical at the time and is still mildly controversial today, but it has become much more widely accepted since we know for a fact that sugar causes inflammation.16 Even small spikes of blood sugar have a particularly bad effect on your vascular system (and raise your cancer risk, too).17 I grabbed the magazine, went home, and made a smoothie out of cottage cheese and orange juice. I had no idea what I was doing! But that gross smoothie still had fewer carbs than I was used to eating in my efforts to get healthy.
I started eating more protein and avoiding grains and most obvious sources of sugar, for the first time focusing more on what I didn’t eat (carbs) than how much I ate. In three months I lost fifty pounds, but more surprising were the changes to my personality. Everyone in my life noticed that I was a lot nicer, and I actually started to develop friendships. I had changed my biology enough that I wasn’t exhausted all the time, and my brain was able to learn how to connect with people, even though it still didn’t come naturally to me. My focus in class also improved, and my GPA went up dramatically, from a 2.8 the previous semester to a double course load with a 3.9.