Dave Asprey - Super Human

Finally, there’s piperlongumine (PPL), a pepper root extract that’s commonly used in Ayurvedic medicine. It looks promising for reducing senescence, but this knowledge is so new that researchers don’t yet understand the mechanism of action. 15PPL may also have cancer-fighting properties, too, although research hasn’t yet confirmed that benefit. 16It is likely safe to use, but taking it all the time or taking high doses could put a load on the liver. If you do decide to use PPL consistently, your body might have a reduced capacity for detoxing 17—so it’s a good idea to take it for a limited period (one to two months) in conjunction with a liver-supporting supplement like glutathione.

It boils down to this: If you don’t want to die, you must make sure your cells do die when they’re supposed to and stay alive when they’re supposed to.

PILLAR 4—CELLULAR STRAITJACKETS

The space in between your cells contains a network of proteins called the extracellular matrix, which protects your tissues from stress, trauma, and even gravity while allowing them to do their jobs. Visualize a perfect wobbling bowl of Jell-O. Without the matrix, you’d just have weird red liquid. Now imagine that same bowl of Jell-O, but so hardened that it won’t wobble and you can’t even spoon it. That’s what anti-aging scientists call extracellular matrix stiffening.

Not only does 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. 19They 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. 20This 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.