What is autophagy and how can you induce it?

Short Answer: Autophagy is the cell's recycling system — it degrades damaged proteins and organelles. It declines with age and can be induced by fasting, rapamycin, spermidine, exercise, and coffee.

Evidence Level: strong

Detailed Answer

Autophagy (from Greek 'self-eating') is a conserved cellular process where damaged proteins, dysfunctional mitochondria, and protein aggregates are engulfed in double-membrane vesicles (autophagosomes) and delivered to lysosomes for degradation. Yoshinori Ohsumi won the 2016 Nobel Prize for elucidating autophagy mechanisms. Autophagy declines with age, contributing to neurodegeneration (failure to clear amyloid-β, α-synuclein, TDP-43) and cancer (failure to remove damaged organelles). Induction strategies: (1) Fasting/caloric restriction — the most potent natural inducer; 24-48h fasting strongly activates autophagy. (2) Rapamycin — directly inhibits mTORC1, the master autophagy suppressor. (3) Spermidine — induces autophagy via EP300 acetyltransferase inhibition. (4) Exercise — activates AMPK-dependent autophagy. (5) Metformin/berberine — via AMPK activation. (6) Coffee — chlorogenic acid and caffeine activate autophagy. Timing matters: autophagy needs to be cyclical, not constant.

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