Proof in Humans that Inhibiting mTOR Prolongs Healthy Life by 11%

Scientific proof exists that optimal medical therapy (OMT)can extend healthier human life by 8 years now. In the last post there was a podcast from Dr Peter Attia with Dr. David Sabatini and Dr Matt Kaeberlein. Dr. Matt Kaeberlein on that wonderful podcast discussed a study in dogs designed to show a 9% longevity increase due to inhibiting the mechanistic target of rapamycin (mTOR) with rapamycin. mTOR is a master metabolic genetic switch that coordinates food availability with growth rates in the fetus and child. Activating mTOR later in life makes us age faster and get sick sooner. There is a study in humans with type 2 diabetes and chronic kidney disease that provides 21 years of follow-up. The average age of entry into the human Steno-2 study was 55 years. After 21 years of follow-up, the average age was 76. Healthy life was extended 8 years or nearly 11% in these people by using OMT interventions that inhibit mTOR compared with those receiving usual care.

The Steno-2 study used a protocol that combined diet, exercise, lisinopril or losartan for hypertension, statins for high cholesterol, and metformin for glucose control with an aspirin and counseling to help stop smoking cigarettes. Oxidants activate growth factors which also increased mTOR activity. Lisinopril, losartan, statins, metformin, and stopping smoking are antioxidants that reduce growth factor signaling which increases mTOR activity. There is every reason to think that we can do even better. We have learned since the Steno-2 study that medications like spironolactone and eplerenone also reduce oxidant-driven growth factor signaling and that metformin inhibits mTOR directly through the critical nutrient sensing mechanism.

There are at least four factors that seem to be consistently involved in more rapid aging and earlier onset of chronic diseases. These are excess oxidant production, a related increase in inflammation, increased mTOR activity, and reduced AMPK activity. The treatments used in the Steno-2 protocol are antioxidants that inhibit mTOR and activate AMPK. AMPK activity is linked to mTOR activation. When mTOR is more active, AMPK is less active. Like mTOR, AMPK is also a master metabolic genetic switch related to food availability. When food is scarce, AMPK functions as a survival switch to help the fetus and child live until food is available again. AMPK activation serves as a survival switch throughout our lives. Metformin directly activates AMPK. Jardiance does the same thing. Diet, exercise, and intermittent fasting also deactivate mTOR while activating AMPK.

With the advantage of this new information, we should be able to increase the human healthspan even more than 11% with medications that have been used for decades and cost about $50 a month. We have broad experience with their effects and side effects. The Steno-2 protocol prolonged life in people who were 55 years old when they entered the study, and they were already very high risk. Even though chronic kidney disease is relentlessly progressive, most patients don’t end up on dialysis because they die of heart attacks and stroke before dialysis is needed.  We are not sure about the dosing of rapamycin. Should we take it daily or weekly and at what dose? These factors are completely worked out in the Steno-2 protocol. Rapamycin is also relatively expensive at five dollars per milligram. If the dose is 8 mg. a week, that is $160 every 4 weeks.

There is a good possibility that starting these interventions earlier would also be more effective. Begin with losartan and add eplerenone as the second drug in high blood pressure management. High-risk patients for cardiovascular events should be on a statin. Metformin is effective in delaying diabetes in prediabetes.

If you look at the diagram above, you can see how this all ties together. A large body of evidence supports the key role of mTOR in aging and chronic disease. The same can be said for oxidants, growth factors, and AMPK. Addressing these realities of epigenetics and molecular biology is at least as important as lowering the sugar, pressure, and cholesterol. Incorporating these concepts into chronic disease management should be a priority for the country.