The Chemistry of Aging (or not!)

There are 12 known pathways of aging.

1st Pathway of Aging: Glycation

Glycation is the bonding of glucose to proteins. It is a normal process of life happening in all of us around the clock, yet a very destructive one. Proteins are our cellular engineers. They’re precision molecules that orchestrate our body chemistry much like employees operate a company. We have thousands of different proteins in our bodies and each one has a unique structure and function.
Glucose is the primary sugar used by our cells for fuel. Therefore, it is constantly mixing with proteins in our blood stream and in the soup within our cells. The glucose molecules have an attraction to our proteins so will bind to them whenever a random collision occurs between the two, which is happening constantly at a very high frequency. As a result, our proteins become bound to sticky glucose and then the proteins begin to stick together to form destructive molecules called AGEs (ay-gee-ees), short for Advanced Glycation Endproducts. AGEs are garbage molecules that gum up our cells and our organs, accelerate aging and hasten our progress toward the age-related diseases.
At the Leonardi Institute, we measure glycation and teach our patients the nutritional maneuvers to minimize it, along with the right type and timing of exercise, specific nutritional supplements and, if needed, medication to limit glycation and AGE formation. This typically results in a 40 to 60% reduction in AGEs from upper normal to the optimal level, slowing aging and reducing disease risk. We’ll go into greater depth in a video coming soon!

2nd Pathway of Aging: Excessive Oxidative Stress

Oxidation is integral to normal body chemistry and is healthy – up to a point. Beyond that point it becomes destructive. Our modern industrial lifestyle takes us well beyond that point. Oxidation is the loss of an electron from an atom. Once the electron is lost, the oxidized atom is called a free radical. It immediately steals an electron from a neighboring atom and the neighbor becomes the free radical. The neighbor then does the same thing, creating a rapid fire, chaotic series of electron transfers in our cells and organs. With each electron transfer comes a potential structural change in the molecule in which that atom takes part. These structural changes can damage DNA, creating a cancer. Oxidation is also the first step in heart disease because LDL cholesterol becomes oxidized prior to forming plaque. And oxidation causes dementia because our fragile brain cells will die when electron transfers reach a particular threshold. The average human body contains seven octillion atoms (7,000,000,000,000,000,000,000,000,000). That’s a lot of electron transfers. But it’s only the excessive oxidative stress that ages us and increases disease risk. At LI, we teach our patients the lifestyle maneuvers to reduce oxidative stress, including the safest water sources, antioxidant foods and nutrients and additional lifestyle maneuvers. With repeated coaching this becomes second nature. Aging is slowed and disease risk plummets. We’ll go into greater depth in a video coming soon!

3rd Pathway of Aging: Depletion of NAD+

Chemically speaking, the aging process kicks in at about age 29. This 3rd primary pathway of aging is the depletion of a compound in the nucleus of our cells called NAD+. Just like your car burns gasoline for energy, our bodies burn ATP. ATP is manufactured in the mitochondria, energy factories within our cells. Our mitochondria are kept robust and productive by NAD+. Children have boundless energy because they are replete with NAD+ and their mitochondria are robust. The more we age, the less NAD+ we retain and the less ATP we’re able to make. The result? Energy depletion. This is not just the energy that you feel when you wake up refreshed or down a cup of java. It’s the ATP required to keep our cells functioning in a healthy, youthful state, free of disease risk. Since 2013 studies have shown that NAD+ levels within our cells can be bolstered and replenished. At LI, we teach the lifestyle maneuvers to replenish NAD+ and use the nutritional supplements that provide our cells with the raw materials to manufacture more NAD+. The result is higher NAD+, robust mitochondria at any age, slower aging and reduced disease risk. We’ll go into greater depth in a video coming soon!

4th Pathway of Aging: Suppression of AMPK

We discussed in the third pathway that our mitochondria are our energy factories. But to make a great product (in this case ATP), we need not only a state-of-the-art factory but also a strong, reliable supply chain of raw materials. Intuitively, we would think that simply means plenty of food. In reality it’s quite the opposite. Studies on every species ever tested show that calorie restriction boosts NAD+ and also reverses this 4th aging pathway by activating AMPK. AMPK is an enzyme in our cells that directs where foodstuffs are sent, i.e., into storage for a rainy day, or directly into our mitochondria for ATP production. Things like exercise and calorie restriction activate AMPK because our cells interpret these maneuvers as “adversity”. These “adversity mimetics” boost NAD+ (pathway 3) and activate AMPK (pathway 4). Other adversity mimetics include flavonoid and polyphenol plant compounds like curcumin, quercetin and pterostilbene. Another is a prescription medication called metformin. We have all of these at our disposal and use them to customize your program for the optimal benefit. We’ll go into greater depth in a video coming soon!

5th Pathway of Aging: Depletion of Glutathione

Oxidative stress, or the excessive creation of oxygen free radicals, has been considered one of the leading pathways of aging for decades. See Pathway #2, above, for a review. Antioxidants are molecules that have an extra electron in their structure, which they’re able to donate to neutralize a free radical. This stops the electron transfers and helps protect DNA from related damage. Well known antioxidants include vitamins C and E and beta carotene. Glutathione is the undisputed most important endogenous antioxidant in the human body. A series of studies between 2019 and 2022 by the Baylor College of Medicine showed that older folks have about 70% less glutathione than young adults. If glutathione is taken as a supplement, it is destroyed and rendered useless by our GI tract. However, the Baylor researchers were able to increase glutathione levels in subjects 70-80 years old, back to the level of subjects aged 20-30. They accomplished this by supplementing a combination of N-acetyl cysteine and glycine, the two amino acid precursors to glutathione production in humans. The results were profound. Ostensibly, bringing the glutathione (natural antioxidant) level into balance with ongoing oxidative stress seemingly reversed aging, causing dramatic reductions in oxidative stress and inflammation along with increased upper and lower extremity strength, faster walking speed, smaller waist circumference, lower systolic blood pressure, an increase in insulin sensitivity, autophagy (explained below) and mitophagy (explained below), AMPK activation and purging of senescent cells. Replenishment of glutathione, therefore, is one of our primary goals at LI. We use NAC along with a proprietary blend of glycine and the cofactors the body uses to make glutathione, all in customized dosing.

6th Pathway of Aging: Failure of autophagy.

Imagine cleaning your living room and finding enough quarters under the cushions of your sofa to buy a new widescreen smart TV. Autophagy is just such a situation for our cells. It is the recycling of old, misfolded or otherwise damaged proteins that are lying about the cell amounting to garbage. In the first pathway of aging, we referred to one type of such garbage: AGEs. In autophagy, AGEs and other garbage proteins are engulfed and digested by structures in our cells called lysosomes. Then the resulting amino acids and peptides are recycled in a manufacturing process to create new, healthy, functional, youthful proteins for optimal cell function. Our Western, sedentary, processed food and high-sugar lifestyle completely silences Autophagy. On the other hand, autophagy is triggered by adversity mimetics such as fasting, exercise and cold exposure. It is also ignited by other techniques we’ve already discussed such as replenishing NAD+ and glutathione and activating AMPK. You see, these age-reversal modalities are all interrelated! Those we activate will facilitate activating others. Before you know it, like a snowball rolling downhill, cellular rejuvenation is going gangbusters. It’s no wonder, then, how we can manage to influence aging so effectively!

7th Pathway of Aging: Failure of mitophagy.

Now that you understand autophagy, mitophagy is an easy one. Mitochondria are structures within our cells that manufacture energy. Sugars and fats are broken down within our cells to very specific, high-energy density molecules that are admitted into the mitochondria. The mitochondria contain membranes that act as assembly lines for energy production. It’s called the electron transport chain and it passes the high-energy compounds from station to station until our ultimate energy source, called ATP, is produced. We run on ATP much like an electric car runs on batteries or an ICE car runs on gasoline. As we age, our mitochondria also become congested with garbage. Mitophagy is the recycling of this garbage within our mitochondria resulting in a cleaner, leaner, meaner, more youthful, efficient energy factory for the production of ATP. Like autophagy, mitophagy fails with age. It is regenerated by the same modalities that spark autophagy. Our cells and their energy factories get spic and span together.

8th Pathway of Aging: Accumulation of Senescent Cells

Nearly all of our cells are programmed to duplicate themselves through cell division, giving birth to daughter cells that take up the cause when older cells die. Older cells die after a finite number of cell divisions. They’re then broken down and their parts are recycled. Some cells, however, for reasons not completely understood, refuse to die. They linger in our tissues in a dysfunctional state and create caustic chemicals called cytokines. They release these cytokines into the surrounding tissue creating inflammation and accelerating the aging process within the organ. These cells are called senescent (old) cells and their state of function is described as “SASP” or senescence-associated secretory phenotype. Remarkably, senescent cells can be nudged into death by certain molecules. One such molecule is a drug used to treat leukemia called dasatinib. Its toxicity is a limiting factor in its use. Much safer molecules derived from plants and known to be safe, can also purge senescent cells. These include flavonoid compounds called quercetin and fisetin. At LI, we employ these safer plant compounds to purge senescent cells. Evidence also supports that replenishing glutathione (pathway 5) also purges senescent cells.

9th Pathway of Aging. Activation of mTOR.

In the 1990s, two mammalian genes were discovered that control growth and development: mTOR (mammalian (or mechanistic) Target of Rapamycin. The mTOR genes are sensitive to energy states and when energy is plentiful, they engineer growth by increasing protein synthesis and increasing the responsiveness of our cells to insulin and growth factors such as IGF-1, all of which is great in youth, when growth and development are so important. However, when we’re older it’s not our friend. mTOR was subsequently shown to aid in the growth and spread of cancer. mTOR activity promotes aging and the inhibition of mTOR has been shown to extend lifespan in mice. mTOR activity also blocks autophagy (cell cleanup – see above). We stimulate mTOR with abundance mimetics like higher food (and especially protein) consumption and a sedentary lifestyle. Scarcity mimetics (calorie restriction, fasting, exercise), on the other hand, inhibit mTOR. Since there is so much cross-talk among the aging pathways, we can also inhibit mTOR by most of the modalities that inhibit the other 11 aging pathways. mTOR can also be inhibited by some nutritional supplements, the diabetes medication metformin and the powerful immune-suppressant drug, rapamycin. While we’re not fans of rapamycin due to the risk to our immune system, we attack mTOR with all the other known modalities.

10th Pathway of Aging: Inflammation

Most of us are aware that inflammation is associated with illness and injury but unaware that it also contributes to aging and the development of age-related diseases. The easiest way to get the picture is to understand what inflammation is: It’s the involvement of our immune system to get rid of bad guys (like viruses or bacteria). Our immune system does this by attacking the perpetrators with chemical warfare: caustic chemicals called cytokines that destroy viruses and bacteria. But chemical warfare causes collateral damage. These cytokines are released into our tissues and blood stream also damaging our healthy cells and organs. The collateral damage from cytokines accelerates aging. Inflammation is turned on by unhealthy lifestyle maneuvers like processed and other junk foods, lack of exercise, obesity, alcohol, and especially smoking. Inflammation can be minimized with an anti-inflammatory diet and regular exercise, along with anti-inflammatory supplements such as clean fish oil and others. Inflammation is also reduced by inhibiting the other 11 aging pathways. At LI, we’re all about anti-inflammation with the right supplements and, of course, ongoing lifestyle coaching.

11th Pathway of Aging: Uncoiling of DNA

Our DNA is a long chain of base pairs of molecules called purines and pyrimidines. There are 4 different molecules: adenine, guanine, cytosine and thymidine (a, c, g and t). If unraveled and stretched out, each strand of DNA would be six feet long! To exist microscopically in the nucleus of our cells, clearly it is tightly coiled. This is important because the tight coiling keeps healthy genes on our DNA active and keeps unhealthy genes dormant. But with aging, our DNA begins to unravel. As it does, healthy genes become dormant and unhealthy genes are more expressed. The result is more rapid aging and increased disease risk. Here’s where the other 11 pathways of aging come into play the most. When they’re managed, our DNA retains its tight coiling and only our best genes are expressed. When they’re ignored, our DNA coils loosen, reducing the expression of healthy genes and increasing the expression of the nasty ones. This is especially and most particularly related to pathway 12.

12th Pathway of Aging: Depletion of Sirtuins

Sirtuins are the guardians of our DNA. They’re proteins that live along our coiled DNA to keep the coils tight so only our best genes are expressed for optimal health. But sirtuins have another function. They’re also responsible for repairing our DNA when damaged (by oxidative stress, inflammation and all the pathways above). To make the necessary repairs, sirtuins must leave their home base where they’re guarding our DNA coils and travel to the site of damage. After the repair they migrate back home. But they’re poor navigators and often don’t make it home, stopping randomly in the wrong place along our DNA to remain useless. By the time we’re 29 years of age, we are significantly depleted of sirtuins. And this is the reason our DNA uncoils with age (pathway 11 above). Sirtuins can be replenished and supported by reducing DNA damage, and inhibiting the other 11 pathways above, particularly by replenishing NAD+ and glutathione and activating AMPK.

Do you find all this confusing and exhausting? Aging doesn’t care. It only follows the chemistry, whether you orchestrate it intentionally or unintentionally. This is where the Leonardi Institute comes in. We have your back in managing all 12 of these aging pathways for optimal vitality, longevity and disease prevention. If the buffalo herd is stampeding off the cliff, do you want to be a normal buffalo? Don’t wait for the cliff to be above you. Cut yourself out of the herd now. Join us for an exceptional life! We’re here for you!