The Master Metabolic Genetic Switches of Life and Death

Epigenetics for Dummies

At the moment of conception, the fertilized human egg becomes a cell with no other function but to make more cells that become teeth, hair, and eyeballs. That fertilized egg contains all the genes and DNA needed to develop a perfectly healthy young man or woman. Every cell has the same genes and DNA. The difference in cell structure and function is the result of gene regulation or epigenetics—switching genes on and of at just the right time, in just the right place, with the right intensity and the right duration. That is the path to normal, healthy development.

There are two master metabolic genetic switches that play a central role in the key processes of life, death, chronic disease, and aging. Let’s call one of the switches the growth switch. Science nerds like me call it mTOR. (lower left part of diagram) The growth switch is vital for normal growth in the fetus and child. The growth switch coordinates food availability with the rate of growth in children.

The other master metabolic switch is the survival switch. Science nerds like me call it AMPK) and it is linked to the growth switch. When there is plenty of food, the growth switch is is flipped on and the survival switch is switched off. When there is no food, the growth switch is flipped off and the survival switch is flipped on.

The survival switch activates dozens of genes that pull calories from fat and muscle to provide the energy for the brain and heart to continue working so that the child survives. The survival switch shuts down the synthetic processes that are not needed to just sustain life like making cholesterol and triglycerides. These two switches exist to assure development and survival of a healthy young adult.

When the child is grown, the core work of these two switches is done, but they continue to do what they were designed to do. More food switches the growth switch on and less food switches it off, but now instead of supporting normal, coordinated growth in the child, it makes the heart bigger and the arteries thicker contributing to the development of high blood pressure. The growth switch is on and the survival switch is off in diabetes, high blood pressure, and heart artery disease.

Oddly enough, the survival switch function persists. It supports longer, healthier life. Everything that prolongs healthy life—eating fewer calories, intermittent fasting, and exercise— switches off the growth switch and switches on the survival switch. Certain medications that reduce all-cause mortality and also prolong healthy life have this same effect. Empagliflozin (Jardiance) switches on the survival switch. Metformin directly flips the growth switch off while switching the survival switch on. As you can see from the diagram, lisinopril, losartan, statins, spironolactone, and eplerenone do the same thing indirectly by blocking excess oxidant production.

These two switches are the final common pathway involved in normal growth, aging, and chronic disease onset. When we use protocols containing the medications and lifestyle measures I have listed, patients with type 2 diabetes and chronic kidney disease live 8 years longer. Now you can understand why patients taking empagliflozin slow the progression of chronic kidney disease and reduce hospitalization by 30% whether they are diabetic or not. Genes that are essential to normal development make us age and get sick faster later in life. If you want to be healthier longer, this science will help.