The Wall Street Journal published this story on Monday, May 1: Can a Kidney Transplant Drug Keep You From Aging? They are talking about rapamycin. Rapamycin is a naturally occurring antibiotic made by bacteria that was discovered on Easter Island. Rapamycin inhibits a master metabolic genetic switch called the mechanistic target of rapamycin (mTOR). That switch is essential to fetal and childhood development. It coordinates the food supply with fetal and childhood development. If mTOR malfunctions in the fetus, the fetus dies early on. For simplicity, lets call this the food-growth switch.
The food growth switch is connected to another master metabolic genetic switch (AMPK) When food switches mTOR on, AMPK is switched off. When there is no food, AMPK is switched on and mTOR is switched off. Starvation switches on AMPK to mobilize calories from muscle and fat to provide enough energy for the fetus and child to survive until there is food again. Let’s call AMPK the survival switch.
The food-growth and survival switches relationship is one of the most fundamental in human biology. It is essential for normal growth, development, and survival in the young. Later in life, mTOR activation still causes growth but it makes the heart bigger and the arteries thicker. Persistent mTOR activation supports cancer growth and more rapid aging. mTOR, caloric restriction, and intermittent fasting switch on AMPK.
AMPK still provides a survival function later in life. It switches on genes that protect cells and organs. It is already possible to prolong healthier life in humans by 8 years by combining medications that directly switch off mTOR and switch on AMPK. Rapamycin and metformin directly inhibit mTOR. Jardiance and metformin directly switch on AMPK. Lisinopril, losartan, statins, and spironolactone indirectly switch off mTOR and switch on AMPK. Diet and exercise switch on AMPK. Every intervention that protects cells and organs more than the lowering of the target risk factor impacts these critical switches. Combining these interventions is best practice. It is optimal medical therapy. It is precision medicine. They are available now to prolong your healthy life at very modest cost.
If I'm reading right, metformin is great in both directions: directly inhibiting mTOR, and directly switching on AMPK. Also lots of other good suggestions.
The mTOR inhibiting function of rapamycin is remarkable. Not only does it look like it will potentially extend life and suppress cancer growth it has also been shown to improve member in older rats given rapamycin. The potential for this could be absolutely huge.
https://mattcook.substack.com/p/how-to-stop-and-slow-down-dementia