Oxidation

Thought food

There is agreement that the enzyme mTOR is the primary driving force of aging, the “Grand ConducTOR” of aging, if you will. (mTOR also seems to activate the joker in study authors: “TOR and the victory over aging” or, my favorite, “TOR’s magical hammer.”) Inhibiting mTOR may interrupt a multitude of degenerative processes more strongly than any other single anti-aging strategy, which explains why the mTOR blocker rapamycin is currently the most effective pharmacologic approach against aging. Nonpharmacologic approaches against this “pacemaker of aging” include restricting certain amino acids like methionine and leucine, general protein restriction, or complete dietary restriction.

To slow this pathway of aging, you should daily:

Oxidation

Earl Stadtman, a highly honored biochemist and recipient of the National Medal of Science, the highest award for scientific achievement in the United States, once said: “Aging is a disease. A person’s lifespan corresponds only to the amount of free radical damage that accumulates in the cells. Once enough damage has accumulated, the cells can no longer live properly and give up.”

This concept, formulated in 1972, is today known as the mitochondrial theory of aging. It posits that over time free radical damage to our mitochondria leads to loss of cellular function and energy. Mitochondria are the power source of cells. It’s like a cell phone that you recharge over and over: Each time, its capacity decreases. Similarly, damage from free radicals accumulates in our power plants, the mitochondria, and over time the mitochondria lose their power.

The greedy Hulk

As a reminder of what free radicals are and how they are formed, take a look at my comic depiction of the quantum biology of oxidative phosphorylation in the chapter on brain diseases in How Not to Die. In short, free radicals are primarily unstable, highly reactive molecules with an unpaired electron.

Electrons, tiny building blocks of matter, like to travel in pairs. Free radicals try to find a partner for their lonely electron by stealing electrons from any molecule that crosses their path. This can have various consequences depending on what kind of molecule gets robbed. If fat is attacked, cell membranes can be destroyed. If enzymes are the victims, they can be inactivated. If other proteins are damaged, they can fall apart and create new structures that our own immune system attacks as foreign bodies, leading to a form of autoimmune inflammation. And when free radicals rip electrons out of DNA, genes can mutate and DNA strands can literally break. Fortunately, our body can defend itself against this, namely with antioxidants, which donate excess electrons and thereby neutralize free radicals without being harmed themselves.

The imbalance between excess free radicals and insufficient antioxidant defenses is called oxidative stress. If one follows the theory, the resulting cellular damage causes aging. Growing older and disease are thus understood as oxidation of the body. You know the brown age spots on the backs of the hands? That is oxidized fat and protein under the skin. It is suspected that oxidative stress is the reason we get wrinkles and become more forgetful, and why our organ systems break down as we get older. Overall, according to the theory, we rust. (Rust is the oxidation of metal.) That would be a reason to eat more antioxidants, but does that actually work? Despite 20,000 published reviews of more than a quarter million papers on antioxidants, the topic remains controversial. Let’s first look at whether the oxidation-and-aging theory is even true.

The only theory that explains the spread

There are more than 300 theories about aging. Although none is generally accepted, the mitochondrial theory gains some weight from the fact that it has held up for almost half a century. Its origins are even decades older than Stadtman’s hypothesis from the 1970s and go back to the time when scientists noticed a parallel between numerous signs of aging and DNA damage from radiation injury. This led in 1956 to the free radical theory of aging, the idea that aging is due to the accumulation of oxidative tissue damage. When it was recognized that mitochondria are the main source of cellular free radical formation, this became the mitochondrial theory.

Any successful theory of aging must solve the fundamental puzzle: Why does lifespan vary so widely among animals? In mammals, it varies by about 200-fold. Some shrews live only a year, whereas Greenland whales reach 200 years or older—and they are only the second longest-lived animal. The ocean quahog in the North Atlantic can live more than 500 years. That is thousands of times longer than some other invertebrates that survive only a few days. Only one of the theories of aging unites the known parameters that explain this range: the mitochondrial theory.

This theory posits that animals live longer the fewer free radicals their mitochondria produce. This is not a question of metabolic rate. Bats and birds, for example, have a fast metabolism but a relatively high life expectancy. The mitochondria of longer-lived species simply seem to work more efficiently. They lose fewer electrons, so there is less oxidative damage to mitochondrial DNA. (Mitochondria have their own small DNA rings, which are generally assumed to encode only 13 proteins, and which are separate from most of the DNA code of the more than 20,000 genes in the cell nucleus.) Fortunately, mitochondrial performance is not an unchangeable constant. We could reduce their production of free radicals with exercise or with a dietary trick: We lower intake of the amino acid methionine.

How to consume less methionine

The methionine content in tissue is closely linked to the maximum lifespan of mammals. The lower the methionine, the higher the life expectancy. This supports the mitochondrial theory, because methionine is the protein component that is most susceptible to oxidation. High methionine levels not only make you sensitive to oxidative stress—they actively cause it. This can be demonstrated in the test tube. If you drip methionine onto isolated mitochondria, they begin to spew out more free radicals. Researchers examined whether this can be dialed down with diet.

In rodents, a 40-percent food restriction reduces the production of free radicals by mitochondria and extends lifespan. The reason, it was found, was the reduction in protein intake. The diet did not have to be restricted overall, because lowering protein alone had the same effect, whereas restricting fat or carbohydrates had no effect on either the formation of free radicals or life expectancy. The positive effects of protein restriction on mitochondrial function, in turn, were based on reducing the amino acid methionine. Restricting all amino acids except methionine had no effect on the emergence of mitochondrial free radicals or on DNA damage, but restricting methionine alone achieved both. This led to the conclusion that mitochondrial electron leakage is controlled by the amount of methionine in the diet.