On January 17, 2024, I started a series aimed at helping you understand the new science of aging and chronic disease. My purpose is to help you understand that medical science has never offered more promise, and this is something that you can easily understand. We don’t just wear out. Gene regulation determines how fast various organisms age, and you can influence that by the way you live and with certain medications. You have learned a lot about how the pieces of this work. Now we will tie it all together, and you will be able to stay healthier longer pretty easily.
mTOR and AMPK
Look at the diagram above. The final common pathway that governs aging is in the lower left corner of the diagram. Everything upstream funnels through the mammalian target of rapamycin (mTOR) and AMPK. These are the two master metabolic genetic switches that control aging and every chronic disease that I have examined. Each of these switches is like a dimmer switch for a light. You cannot live without some small amount of mTOR activity, but too much will kill you and in many cancers mTOR is persistently set at maximum brightness.
This is a great example of a fundament principle. Faster aging and chronic illnesses are not usually caused by abnormal genes, they are caused by abnormal gene regulation or epigenetics. In the human fetus and child, mTOR coordinates food supply with growth. mTOR is the growth switch. It is linked to another master metabolic genetic switch, AMPK. When there is no food, mTOR is minimized and AMPK is maximized. AMPK is the survival switch. When there is no food, AMPK pulls calories from your fat and muscle to provide energy so that you can find food and survive. The more the AMPK switch is activated, the less cholesterol we make. We stop making things and growing. The entire focus is on survival.
Once we become adults and stop growing, the healthiest state is lower mTOR intensity and greater AMPK activity. Overeating all day still activates mTOR, but in adults more active mTOR makes us age faster and get sick sooner. AMPK continues to be a survival switch throughout life.
Growth Factors
Now look right in the middle of the diagram and you will see the box labeled EGFR. That is another master genetic switch box. That box represents growth factors and growth factor signaling. That is another coordination point for normal growth that produces faster aging and chronic disease later. You can see there are two pathways below the growth factor box and these boxes contain proteins formed by genes that work like dominoes. It you activate growth factor signaling, you knock over the Ras/Raf/Erk1/2 protein dominoes that activate mTOR. The left line of dominoes works the same way.
Increased growth factor signaling is another way to activate mTOR and deactivate AMPK. In the normal fetus and child, numerous growth factors come in at just the right time, in just the right place, with just the right intensity, and for exactly the proper duration to form a perfect healthy young adult that can produce other children. That is the entire purpose of our genetic code. Later in life, poor diet, cigarette smoke, and abdominal fat switch on this growth factor signaling to make us age faster and get sick sooner.
Growth factor signaling is another way to amplify mTOR activity with food. We discussed the growth factor insulin in some detail. Insulin levels go up when we eat carbs and sugar, and they are chronically higher if we have too much belly fat. In the fetus and child, more food and higher insulin levels lead to faster growth. Higher insulin levels lead to increased mTOR activity.
Growth factors also contribute to disease. If a man has a blockage of urine flow due to an enlarged prostate, the bladder muscle will grow to provide more bladder contraction force to push the urine out. One of the epidermal growth factors activates the epidermal growth factor receptor (EGFR) to drive that muscle growth. In diabetic eye damage, vascular endothelial growth factor (VEGF) is increased and that causes the tiny vessels in the retina to grow which often leads to blindness. Monthly injections of an antibody against VEGF (Avastin) slow down the vessel growth and preserve vision. This science is very practical here and now.
Oxidants and Antioxidants
Growth factor signaling that increases mTOR activation is an important way that oxidants make us age faster and get sick sooner. Oxidants activate EGFR directly without involving a growth factor. So, you can easily see from the diagram that the oxidants in cigarette smoke activate EGFR and then mTOR. The oxidants produced by overeating do the same thing.
The part of the diagram above EGFR shows you that genes in abdominal fat that increase our blood pressure and cholesterol also lead to excess oxidant production that activates EGFR and then mTOR. Losartan and eplerenone for blood pressure and statins for cholesterol very precisely block this oxidant production. That is how they reduce inflammation and protect our organs and cells far more than they lower the target risk factor.
This one diagram has it all. You can see at a glance how virtually all (all?) factors that make us age and get sick faster funnel through the master metabolic genetic switches represented by the growth factor box, mTOR, and AMPK. You can see how extra weight, overeating, cigarette smoke, and abdominal fat all tie together to make us age faster and develop type 2 diabetes, heart disease, and cancer sooner. Sure, there is more to it than that, but these are the central common pathways that drive chronic diseases and aging. Best of all you know now that eating real food, intermittent fasting, and exercise push mTOR and AMPK in the right direction. You also know that the medicines in the green boxes have the same effects as diet and exercise. Now you have it— a unified hypothesis of aging and chronic disease that can make your path to a longer, healthier life much smoother.
MCG Technology directly detects and quantifies the impact on down regulations of mTOR and up regulations AMPK due to fasting/intermediate fasting and the positive effects of various lifestyle optimization. MCG measures one’s cardiovascular physiological functions at the bedside for ten minutes! Help is on the way: https://open.substack.com/pub/mcgdoc/p/what-do-we-do-why-mcg-technology?utm_campaign=post&utm_medium=web
Enjoy the ride!
Drugs should be our second, third, or last resort. Fundamentally, all options, including lifestyle choices, quality of food, environmental conditions, and etc., must be considered and carefully considered, evaluated to determine the merit objectively, and transparently. The problem with pharmaceuticals is that the big pharma has been gaslighting people for decades now to plunder them by focusing on selling drugs and devices that are not safe and effective. They marginalize and censor the lower cost maybe more effective alternatives. The big pharmaceutical industrial complex has been ruining our economy and taking away our freedoms.