Autophagy
Your cells' built-in recycling program. Autophagy (Greek for "self-eating") breaks down and recycles damaged proteins, organelles, and cellular debris. It's essential for longevity, disease prevention, and cellular renewal.
What Autophagy Does
Clears Damaged Proteins
Removes misfolded and aggregated proteins linked to neurodegeneration.
Recycles Mitochondria
Mitophagy removes dysfunctional mitochondria, preventing oxidative damage.
Kills Pathogens
Eliminates intracellular bacteria and viruses through xenophagy.
Provides Emergency Fuel
Recycles cellular components into amino acids and nutrients during fasting.
Tumor Suppression
Removes damaged DNA and defective cells before they become cancerous.
Extends Lifespan
All longevity interventions (caloric restriction, exercise) work partly through autophagy.
How Autophagy Works
Initiation
Nutrient deprivation activates AMPK, inhibits mTOR
Nucleation
Double membrane begins forming around cargo
Cargo Selection
Damaged parts tagged with ubiquitin for degradation
Fusion
Autophagosome fuses with lysosome
Recycling
Components broken down and reused by cell
Types of Autophagy
Macroautophagy
The main type. Bulk degradation via autophagosomes that engulf large portions of cytoplasm. This is what most research refers to.
Microautophagy
Direct engulfment of cytoplasmic material by the lysosome membrane. Smaller scale, continuous process.
Chaperone-Mediated
Specific proteins are recognized by chaperones and directly transported to lysosomes for degradation.
Autophagy Triggers
Fasting (16-24+ hours)
The most potent natural trigger. Nutrient deprivation forces cells to clean house.
Exercise
Both endurance and resistance training activate autophagy, especially when fasted.
Sleep
Overnight fasting during sleep naturally promotes autophagy.
Spermidine
Found in aged cheese, mushrooms, legumes. Induces autophagy via epigenetic mechanisms.
Coffee / Caffeine
Coffee activates autophagy, possibly through AMPK activation.
Resveratrol / Curcumin
Polyphenols that promote autophagy through sirtuin and AMPK pathways.
Autophagy Inhibitors
Constant Eating
Snacking and grazing keep insulin elevated, mTOR active, autophagy suppressed.
High Protein / High Carbs
Both activate mTOR strongly. Protein especially suppresses autophagy.
Insulin / IGF-1 Signaling
Growth signals tell cells to build, not clean. High insulin = low autophagy.
Aging
Autophagy declines with age, contributing to cellular dysfunction and disease.
Chronic Inflammation
Inflammatory signals can impair autophagic machinery.
Autophagy and Disease
Neurodegeneration
Alzheimer's, Parkinson's, Huntington's all involve protein aggregate buildup that autophagy should clear.
Cancer
Complex: autophagy suppresses early tumors but may help established cancers survive stress.
Infections
Autophagy eliminates intracellular pathogens. Some viruses evolved to hijack or suppress it.
Metabolic Disease
Impaired autophagy in liver and pancreas contributes to fatty liver and diabetes.
Heart Disease
Cardiac autophagy maintains heart function. Defects accelerate heart failure.
Aging
All hallmarks of aging involve declining autophagy. Restoring it extends healthspan.
Metabolic Connections
Fasting
Most potent natural trigger for autophagy
mTOR
Inhibits autophagy when nutrients abundant
AMPK
Activates autophagy during energy stress
Mitophagy
Selective autophagy of damaged mitochondria
Spermidine
Induces autophagy by inhibiting acetyltransferases
Resveratrol
Promotes autophagy through AMPK and sirtuins