Toyos Dry Eye Diet (eBook)

Chapter 3

Hormesis

“You may encounter many defeats but you
must not be defeated” Maya Angelou

If data from the blue zone project gives us a bird’s-eye view of what we can do to improve health and DED, work being done by anti-aging scientists give us a view of what is happening at the molecular and genetic level.

Several Nobel Prize-winning discoveries have demonstrated that we have the power to shape our health destiny. We once believed our genetic makeup would dictate your future. Even though we believe in nurture over nature, when it comes to our health we throw our hands up and lament that we were born with bad genes and there is nothing we can do about it. But science has shown us that at the molecular level there is more to the story than just our DNA. We may have DNA that is programmed for disease and aging but there are steps we can take to turn those genes off.

For example, a person with a certain genetic problem may need to avoid a certain food. We are not talking about an allergy here, but a genetic abnormality. For example, if someone with a deficiency in making the enzyme glucose-6-phosphate dehydrogenase (G6PD) were to eat fava beans, they would become sick because the fava bean is high in the glucosides divicine and convicine, and if your body can’t produce G6PD to break them down, the result could be life-threatening. G6PD deficiency is an extreme example, but it underscores the point that our choices can expose problems that otherwise would not be manifest.

IT'S ALL ABOUT THE HOW

Epigenetics is the study of how organisms can change not because of an alteration to the genetic code but by modification of the expression of it.

DNA is wrapped around proteins called histones that give the chromosomes structural support. How it is packed around these histones determines if a particular gene is turned on or off.

We used to believe that some nonsense information at the end of the DNA strands, called telomeres, played no role in expression. The telomere is a cap that protects the end of the chromosome. As we age the telomere becomes shorter until, finally, it erodes to the point where the DNA can no longer work to produce new proteins.

Since the completion of 92% of the total human gene sequence by the Human Genome Project in 2003 researchers have been focused on epigenetics and health. “This foundational information will strengthen the many ongoing efforts to understand all the functional nuances of the human genome, which in turn will empower genetic studies of human disease,” says Dr. Eric Green, director of the National Human Genome Research Institute

Can we use our genetics knowledge to have healthier lives and improve our DED? Nobel Prize-winning work done by Elizabeth H. Blackburn, Carol W. Grieder and Jack W. Szostak demonstrated that we can use the telomerase enzyme to lengthen our telomeres and possibly increase lifespan, for we know that shortened telomere length is associated with cardiovascular diseases, stroke, cancer, arthritis, osteoporosis, cataracts, Type 2 diabetes, hypertension, mental diseases, chronic obstructive pulmonary disease, and dementia. Shorter telomere length leads to decreased cell growth and increased cell death. A healthier lifestyle can activate telomere length as well. I am convinced that improvement in telomerase activity will improve DED. (The Chinese herb astragalus can stimulate telomerase. Astragalus is in my must-have supplements list.)

Are there other lifespan supplements and lifestyle changes that can help with DED? Epigenetics is focused on seven enzymes called sirtuins (named after the yeast SIR2 longevity gene), which are responsible for regulating histones and for turning on and off certain genes. These proteins need the molecule nicotinamide adenine dinucleotide (NAD) to function. If we want to be healthy and improve our DED, we need to keep our sirtuins doing their job of DNA repair.

NAD is important for normal functioning of the mitochondria, the powerhouse of our cells. We know that NAD levels decrease with age. The basal tear secretion also decreases with age. It is not a great leap to think that increasing the NAD in our system will help the meibomian glands work more efficiently. IPL and low-level light treatment (LLLT), works because the wavelengths of light at a specific fluence (power) stimulate the mitochondria of the meibum cells to work better. Patients that I have supplemented with NAD have improved more rapidly with IPL than patients with IPL alone. It is another reason why younger patients responded more quickly to IPL than older patients, because their levels of NAD are naturally higher. DED patients need activated sirtuins to repair their diseased goblet cells, meibomian and lacrimal glands. The sirtuins need NAD. (NAD is another must-have supplement to combat DED.)

As well as sirtuins, another gene also affects health and longevity. The mammalian target of rapamycin, mTOR, is responsible for DNA repair and digesting old proteins and can be used for cell growth or for cell repair. When amino acids are in abundance to make proteins, mTOR activity is spent on growth. When nutrients are scare, mTOR activity is spent on repair and survival.

This knowledge is behind the thought of intermittent fasting or calorie restriction (CR) to inhibit mTOR. When mTOR is inhibited by calorie restriction or by rapamycin, the body goes into survival mode, shutting down activity in the body that is not necessary. When mTOR is suppressed, it will signal the body to begin the process of autophagy (Greek for eating of oneself), breaking down and removing dysfunctional cellular components to conserve energy.

I am often asked if injured meibomian glands can be revitalized. I have seen injured meibomian glands, cornea nerves, and conjunctiva repair after proper treatment with IPL and platelet rich plasma (PRP). We see corneal nerve repair with cenergermin (brand name Oxervate). Adult tissues have stem cells, undifferentiated cells, that can regenerate and differentiate into a specific needed cell type. However, as we age these stem cells can accumulate mutations and lose their ability to function properly. This is where mTOR, depending on the situation, becomes an important factor in the rejuvenation of these stem cells by initiating repair.

COULD WE USE RAPAMYCIN AS A SUPPLEMENT

Rapamycin, also known as sirolimus, is a class of antibiotic that was discovered in 1972 in the soil of Easter Island, which is produced by a bacterium called Streptomyces hygroscopicus. Rapamycin is used as an immunosuppressant for transplant patients and has been shown to increase histone count in gut cells. Our levels of histones decrease as we age making a supplement such as rapamycin valuable.

But there is plenty of conflicting data when it comes to the use of low dose rapamycin for health. For instance, it may cause diabetes. Therefore, rapamycin is not a supplement that I recommend, especially if we can get the same effects with intermittent fasting and calorie restriction.

Anti-Aging science has shown us that stress that doesn’t kill us makes us stronger. I didn’t need this research to prove to me that shocking cells could improve their condition. Our aesthetics clinic provides different treatments that shock the skin to rejuvenate it. In the early days we would blast the skin with light, turning it red for a week. Then the skin would recover and look better. But if too much energy was applied the skin could be burned. One huge discovery was that when our skin undergoes these procedures that produce heat in the inner depths (the dermis), it causes cells to produce heat shock proteins (HSP) that are responsible for repair, and in the end, better functioning of the cells. But when too much heat is produced, the cells stop functioning altogether.

The idea of a level of biological damage or adversity that stimulates repair processes that provide cell survival and improved health is called hormesis.

What can we take to activate our sirtuins and mTOR? On the lifestyle front, exercise and diet can activate the longevity genes, which I cover later in the book. I have already recommended NAD and Astragalus but you can also take resveratrol.

Professor Konrad Howitz found that a polyphenol found in strawberries and butein found in flowering plants, can activate SIRT-1. Resveratrol has the same chemical structure as these, and is found in grapes. Plants have stress molecules, as we do, and grapes produce resveratrol when stressed. Pinot Noir is produced in a stressed soil and therefore produces the most resveratrol.

These molecules from the plant world are called xenohormetic. Other xenohormetic plants and molecules are metformin from lilacs, epigallocatechin gallate from green tea, and quercetin from fruit. I will be recommending foods and supplements that contain these xenohormetic compounds to improve your DED.

Metformin is a prescription drug used to treat diabetes. The benefits of taking metformin for general health are many. One retrospective study showed improvement in the objective measures of dry eye. Metformin can help mTOR by aiding in calorie restriction, it can activate the metabolic control enzyme known as AMPK (AMP-activated protein kinase is a cellular energy sensor when turned on can improve mitochondrial function), and has anti-inflammatory effects on DED inflammatory mediators. It activates SIRT1 and mitochondria.

Metformin lowers blood glucose, but studies have shown that it increases life expectancy, and decreases dementia, cancer,...