Autophagy
The cellular recycling system that activates longevity pathways
Definition
Autophagy (from the Greek for 'self-eating') is the process by which cells degrade and recycle their own damaged or defective components — misfolded proteins, deteriorated mitochondria, intracellular pathogens. This cellular quality-control mechanism is essential for longevity: its decline with age is directly associated with the development of neurodegenerative diseases, cancer, and accelerated ageing.
Detailed explanation
Yoshinori Ohsumi was awarded the Nobel Prize in Physiology or Medicine in 2016 for discovering the molecular mechanisms of autophagy. The process is activated when the cell detects nutrient scarcity (fasting, caloric restriction) or stress: a double membrane called the phagophore forms and engulfs the material to be degraded, creating the autophagosome. This then fuses with the lysosome, where digestive enzymes break down the contents into reusable amino acids and lipids.
The mTOR pathway is the central regulator of autophagy: when mTOR is active (abundant food, high insulin), it inhibits autophagy. When mTOR is inhibited (fasting, rapamycin), autophagy is activated. The protein kinase AMPK has the opposite effect: its activation stimulates autophagy.
In longevity medicine, treatments that stimulate autophagy include intermittent fasting, caloric restriction, high-intensity exercise, NAD+ IV therapy (which activates sirtuins that stimulate autophagy), and hyperbaric oxygen therapy.
Scientific sources
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