Super Human. Dave Asprey
the matrix literally hold your cells together, but it also gives your tissues their elasticity. This is incredibly important, especially when it comes to certain tissues such as those that make up the arteries. When these tissues lose their elasticity, they become stiff, and your body has to work harder to push blood throughout your circulatory system. This can of course lead to high blood pressure and heart disease.
So why does the matrix become so stiff? When sugar in your blood circulates throughout your system, it permanently binds with proteins, creating inflammatory advanced glycation end products, or AGEs. Glycation is the process of sugar bonding to protein. AGEs are aptly named, as these end products accelerate the aging process and create oxidative stress in the body.18
Think about it this way. When you eat something that contains sugar, glucose molecules travel through your body and look for proteins to bind with. Once stuck together, the glucose actually browns the proteins. This is the exact same chemical reaction that takes place when you brown onions in a pan and the sugar and onions become caramelized. When you have high blood sugar, it is at least partially because you made decisions that literally caramelized your insides. Yum. Not really.
There are multiple classes of AGEs. The most abundant in collagen is called glucosepane, and it contributes to diseases of aging from diabetes to vascular dysfunction. Thankfully, researchers are beginning to look for ways to break down AGEs and prevent them from stiffening the extracellular matrix. In 2018, the journal Diabetes reported that scientists had identified four enzymes that are able to break glucosepane cross-links.19 They are still looking at the exact mechanism of action and whether or not the process of degrading AGEs creates other harmful metabolites, but this is a very promising area of research if you have type 2 diabetes or heart disease or just want to avoid this pillar of aging.
Even if, as I predict, glucosepane-degrading enzymes do prove to be safe and effective, it’s better to just avoid extracellular matrix stiffening in the first place. To do that, you must reduce your blood sugar levels, particularly the spike in blood sugar you experience after meals. A study looking at glucosepane levels showed that this harmful AGE pretty much universally increases with age. In a nondiabetic control group, continuous high blood sugar more than doubled levels of this aging substance. Reducing blood sugar is not optional if you want to become Super Human. Fortunately, it’s not as hard as you might think. You’ll learn more about how to do this in chapter 3.
Chronic inflammation of any type is also associated with an increase in cross-linked proteins. This makes sense, since you already know that high blood sugar causes inflammation and high blood sugar causes these cross-links. In addition to managing your blood sugar levels, you should avoid eating foods that make you inflamed. When you are sensitive to a certain food, your body initiates an immune response that triggers inflammation. If this happens consistently, you end up with chronic inflammation and excess AGEs. There are good at-home tests that can help you pinpoint which foods you are sensitive to. I recommend Viome, which you’ll read more about later, and EverlyWell. (Disclosure: While I use both services, I’m an investor in and advisor to Viome, and EverlyWell has advertised on Bulletproof Radio.)
PILLAR 5—EXTRACELLULAR JUNK
As you age, waste products called extracellular aggregates build up both inside and outside your cells. Of the waste products that accumulate outside your cells, the main culprits are dysfunctional, misshapen proteins usually called amyloids. When amyloids start to accumulate, they stick together and form plaques that cause aging and disease by “gumming up the works” and getting in the way of healthy cellular interaction.
You can think of amyloids like the gunk clogging a sink. When you’re young, you won’t notice the impact—a single hair slips easily down a drain. But eventually, as more and more gunk accumulates in the pipes, water dissipates more and more slowly. It’s that gradual process that slowly wears you down as you age.
You’ve probably heard that patients with Alzheimer’s disease have a type of plaque (in this case called beta-amyloids, a type of protein aggregate) in their brains. But long before you develop Alzheimer’s, these same plaques can impair cognitive function. In the case of type 2 diabetes, one type of protein aggregate called islet amyloid inhibits insulin secretion. Protein aggregates also cause stiffening in the heart. This is called senile cardiac amyloidosis and is a major cause of heart failure.
So what causes proteins to stick together in the first place? The problem with amyloids is that they build up in different tissues for different reasons, and we don’t know all the reasons yet. We do know that autoimmunity, when the immune system attacks its own healthy cells, makes it worse, and at least 30 percent of people have some form of autoimmune disease. And recent research on mice links low insulin levels to the formation of amyloids in your brain.20 This is one reason you don’t want to be on an unending low-carb diet that keeps you in ketosis without pause. You’ll live longer if you sometimes eat low carbs, sometimes eat moderate carbs, and always avoid sugar and bad fats. Low insulin is worse than high insulin in this case, but neither will keep you running at your peak.
Even if you don’t have full-blown autoimmunity, inflammation stemming from food sensitivities or even unending emotional stress can lead to amyloid buildup (in addition to AGEs). It appears that amyloids form during long periods of chronic inflammation from any cause. The smart strategy is to reduce your inflammation levels by avoiding foods you are sensitive to and learning how to chill out. If you’re eating food that’s not compatible with your biology, you’re going to end up inflamed, and that will age you in multiple ways. Same deal if you spend a lot of time in a state of stress.
The good news is there are simple strategies you can use to partially break down or reduce the formation of these proteins that age you prematurely. One of the best things you can do is to boost autophagy, your body’s recycling program, by consuming more of the foods you will read about in the next chapter. This will help break down these proteins so they don’t end up forming harmful plaques. So will fasting.
Gordon Lithgow, PhD, a professor at the Buck Institute for Research on Aging, has also found that vitamin D helps prevent proteins from losing their shape and sticking together. With vitamin D deficiency so widespread,21 this raises the question of whether Alzheimer’s rates are increasing in part because people do not have enough vitamin D to slow amyloid plaque formation.
There is also a clear connection between toxic heavy metals and amyloids. A study from the Society for Neuroscience found that excess copper prevented the body from clearing protein aggregates on its own.22 You need copper for many functions in the body, but too much of it is toxic. Medical research shows that the blood vessels and brains of patients with Alzheimer’s disease contain excess copper. Cadmium, another heavy metal, increases the formation of protein aggregates in the brain and appears in greater amounts in brain tissues of patients with Alzheimer’s disease than in healthy brains.23 You’ll learn how to avoid and detox from these metals and others later in this book.
In his lab, Lithgow has demonstrated that chelators, small molecules that bind with heavy metals and help you detox, protect mice from developing protein aggregates. You won’t be surprised to hear that chelating from heavy metals has been a priority of mine for years. You’ll read all about how to do this later. Heavy metal exposure has been on the rise for decades, and no matter where you live or how clean you eat, chances are that you still have higher than ideal levels of metals like lead and mercury. Approximately 6 million pounds of mercury is released into the environment each year, and lead, arsenic, and cadmium are present in detectable levels in our air, water, food, medicine, and industrial products. Even organic kale is high in one heavy metal.
In addition to contributing to the buildup of amyloids, heavy metals also cause mitochondrial dysfunction.24 A small amount of exposure to lead, mercury, nickel, uranium, arsenic, or cadmium for a short amount of time can impair mitochondrial energy production and increase mitochondrial death.25 Even if you don’t realize it, the heavy metals already in your body are likely aging you right now. You’ll learn about how to detox them later.
PILLAR 6—JUNK BUILDUP INSIDE CELLS
Okay,