Topic:
Ben explains how AMPK and mTOR are critical regulators of aging and metabolism, and how their balance can be influenced by diet and lifestyle. Instead of drugs like rapamycin, strategies like carbohydrate restriction and ketosis offer a safer path to optimizing longevity.
Summary:
In this Metabolic Classroom mini lecture, Dr. Bikman explores two of the most important molecular “switches” that regulate how cells age, grow, and repair themselves: AMPK and mTOR.
These pathways operate in a delicate balance—AMPK promotes energy conservation, fat oxidation, and cellular cleanup (autophagy), while mTOR supports cellular growth and protein synthesis. When AMPK is up, mTOR is down, and vice versa.
Ben explains how modern lifestyles—especially chronic overnutrition and excess carbohydrate intake—shift this balance toward persistent mTOR activation, which may accelerate aging and metabolic disease. He critiques the growing popularity of rapamycin for longevity, citing its lack of human data and serious side effects, particularly reproductive harm. Instead, he proposes that simple lifestyle strategies—like carbohydrate restriction, ketosis, and supplementation with ketones like BHB—can more safely optimize the AMPK/mTOR balance.
He also highlights the importance of ketones as both energy sources and signaling molecules that can activate AMPK and stimulate autophagy. The lecture ends with a clear takeaway: longevity and metabolic health may not require pharmaceuticals, but rather informed choices around diet and lifestyle.
summerizer
AMPK and mTOR are the two master switches inside cells that set the balance between repair and growth.
Growth vs repair
- AMPK turns on when energy is low and tells cells to stop building and start repairing.
- mTOR turns on when food is abundant and tells cells to grow, build, and divide.
- Modern life keeps mTOR on all day through constant food, insulin, and growth signals, which crowds out repair.
What AMPK does when it is on
- AMPK is an energy sensor and rises with low cellular energy.
- Autophagy increases, and the cleanup program removes damaged proteins and dysfunctional mitochondria.
- It supports stress-response transcription factors (FOXO and NRF2) and suppresses inflammation.
- A 2012 paper links AMPK, mTOR, and ULK1 as a direct control point for autophagy initiation.
What chronic mTOR does
- mTOR is a growth and nutrient integrator (insulin, amino acids, calories).
- Short, meal-driven mTOR activation supports building, and chronic activation reduces cellular maintenance.
Ways to shift the switch toward repair
- Time between meals moves signaling toward AMPK.
- Lower insulin signaling reduces mTOR activation.
- Protein amount and amino-acid mix matter because amino acids (especially leucine) activate mTOR.
Drug examples in longevity narratives
- Rapamycin targets mTOR, and a 2009 Nature paper shows longer mouse lifespan even with later-life dosing.
- Larger mouse lifespan effects are shown at higher doses in later studies.
- In humans, rapamycin-class drugs are used for transplantation and have reproductive side effects in men and women.
- Metformin is an anti-diabetic drug tied to AMPK, and a Nature paper links metformin binding to PEN2, ATPase inhibition, and AMPK activation without ATP depletion.
Ketones and ketogenic diet signaling
- Beta-hydroxybutyrate (BHB) is a ketone that can activate AMPK and support autophagy.
- A Cells paper links BHB to the autophagic–lysosomal pathway and shows brain changes in mice on a ketogenic diet.
Bottom line
- Aging slows when the cell periodically shifts away from constant growth signaling and back toward repair and cleanup.
References
10,000,000 solar systems with humanity in it and nobody thinks to explore different forms of governance. It's all strong man politics taken for granted.
Benevolent space mind slavery
Benevolent space empire
Benevolent space mutant empire
It's all the same thing....
So if they end up with
Benevolent ai emperor... Fine
I don't fault Asimov, but I'm perplexed at how the story got so popular.