This article is intended solely for informational purposes. It is not meant to be taken as, and should not be construed, as medical advice. Any changes to your lifestyle or diet should be done in consultation with your doctor or health care professional.


To understand the huge amount of information becoming available around life extension and longevity, I find it helpful to think about two biological pathways: mTOR and AMPK.

When I hear about a new approach that supposedly lengthens the lifespan, I try to figure out first which pathway it’s associated with. 


The mTOR pathway is a pathway toward health, but not toward longevity. MTOR activation is associated with:

  1. Being well fed – optimal nutrition
  2. Eating high protein
  3. Eating animal protein
  4. Eating leucine
  5. Higher blood glucose
  6. High insulin 
  7. High IGF-1
  8. Strength training
  9. Strong bones
  10. Powerful muscles
  11. A strong mind. MTOR activation protects to some degree against dementia.

It may sound great from the description above. Who wouldn’t want radiant health and strong muscles? But it’s a pathway toward short lives. Lab animals fed a large amount of protein experience the mTOR pathway. They live what we think of as a normal (short) lifespan. Humans on the mTOR pathway can expect to live a few decades. They often die in their seventies or eighties.

If a food or supplement supports strong bones and muscles, it’s on the mTOR pathway. So I take it with protein, when I’m feasting.


The AMPK pathway stresses our body and activates the SIRTUIN (survival) genes. They’re either on or off; AMPK turns them on, summoning all of our internal resources to deal with perceived threats. Anything that stresses us without killing us, enough to activate our survival genes, tends to fit in this category. It includes things like:

  1. Fasting 
  2. Caloric restriction
  3. Time restricted eating
  4. Alternate day fasting
  5. Prolonged periodic fasting
  6. Fasting mimicking diets
  7. HIIT exercise (creating a repeated oxygen deficit)
  8. Cold thermogenesis: cold showers and baths
  9. Heat shock proteins: Hot saunas
  10. Autophagy: cleaning cellular debris from the body
  11. Apoptosis: cleaning senescent cells from our bodies and brains
  12. Taking supplements for blood glucose: metformin or berberine
  13. Taking NAD boosters: NMN, NR, Niacin (NA), Pau D’Arco and others
  14. Sirtuin activators: Olive oil, resveratrol and pterostilbene
  15. Lower IGF-1 activation
  16. Hormesis
  17. Stress adaptation
  18. The PGS1-alpha gene is activated
  19. Eating lower protein

Lab animals fed less protein, and stressed with fasting, HIIT exercise, heat, cold, and given metformin or berberine and NAD boosters are on the AMPK pathway. They live up to 50 percent longer than their cousins on the mTOR pathway. If a supplement supports the AMPK pathway, I take it when I’m fasting.

MTOR and AMPK are both important. But we can’t just balance mTOR and AMPK equally and expect to live long lives. Anti-aging appears to be taking shape around activating the mTOR pathway enough to stay strong, but being on the AMPK pathway most of the time.

For example, we might be doing alternate day fasting — skipping food one day, and eating within a 10 hour window the next day.  In a two day (48 hour period) we’d spend 10 hours on the mTOR pathway (feasting), and 38 hours on the AMPK pathway (fasting).