The TL;DR
Autophagy (from Greek “auto” = self, “phagy” = eating) is the process where cells hunt down damaged components—misfolded proteins, old mitochondria, viruses—and feed them to the Lysosome (the stomach of the cell). The lysosome breaks them down into raw materials to build new, healthy structures. It is the ultimate anti-aging mechanism.
Accessibility Level
Level 2 (Optimization): You cannot measure it (yet), but you can trigger it via Fasting (Level 1) and specific supplements.
The Science of Recycling
Why We Need It
Cells accumulate trash over time.
- Protein Aggregates: Sticky clumps that cause Alzheimer’s (Amyloid/Tau).
- Lipofuscin: “Age pigment” that clogs cells.
- Dysfunctional Mitochondria: Leaky engines causing oxidative stress.
Without autophagy, the cell becomes a hoarder’s house—cluttered and dysfunctional. Eventually, it dies or becomes senescent.
The Triggers
Autophagy is evolutionarily designed to save you from starvation.
- Nutrient Deprivation: When food is gone (Fasting), the body says “We need amino acids! Break down the old furniture!”
- mTOR Inhibition: As long as mTOR is ON (growth), Autophagy is OFF. You must suppress mTOR to clean house.
Evidence Matrix
| Source | Verdict | Notes |
|---|---|---|
| Yoshinori Ohsumi | Nobel Prize | Won the 2016 Nobel for discovering the mechanisms of autophagy. |
| Ana Maria Cuervo | Expert | Showed that “Chaperone-Mediated Autophagy” declines with age, driving cellular collapse. |
| Guido Kroemer | Expert | Demonstrated that autophagy induction is required for the longevity benefits of caloric restriction. |
How to Optimize
1. Fasting
- 16-18 Hours: Begins the process (mild autophagy).
- 24-48 Hours: Peak autophagy in many tissues. Deep cleaning mode.
2. The “Fast-Breaker”
Don’t break a fast with high protein/carbs immediately if you want to extend the effect. Fat (MCT oil, avocado) stimulates mTOR the least.
3. Autophagy Mimetics
Substances that trigger autophagy even without fasting:
- Spermidine: Found in wheat germ/aged cheese.
- Resveratrol / Fisetin: Polyphenols.
- Coffee: Yes, black coffee stimulates autophagy in the liver/heart/muscle.
4. Sleep
The brain has its own version called the Glymphatic System, which is essentially autophagy for the brain, active only during deep sleep.
References
Levine, B., & Kroemer, G. (2008). Autophagy in the pathogenesis of disease. Cell.
Madeo, F., et al. (2018). Spermidine delays aging in humans. Aging.
Rubinsztein, D. C., et al. (2011). Autophagy and aging. Cell.