Autophagy

TL;DR

  • Autophagy is the body’s natural process of cellular cleanup and recycling, removing damaged proteins, organelles, and pathogens.
  • Acts as a cellular repair and renewal mechanism, supporting metabolic health, immunity, and longevity.
  • Activated by fasting, caloric restriction, exercise, and certain compounds (spermidine, resveratrol, rapamycin).
  • Declines with age, contributing to neurodegeneration, cancer, and metabolic disease.
  • Enhancing autophagy is considered a key anti-ageing strategy in modern longevity research.

At-a-Glance Facts

  • Entity Type: Biological Process
  • Name Origin: Greek auto (“self”) + phagy (“eating”) = “self-eating”
  • Function: Cellular recycling and waste removal
  • Hallmarks of Ageing Impacted: Loss of proteostasis, mitochondrial dysfunction, deregulated nutrient sensing
  • Location: Occurs in all cells, especially active in liver, brain, muscle, and immune cells
  • Research Status: Strong animal evidence; human trials on autophagy enhancers are growing

What is Autophagy?

Autophagy is a cellular maintenance system where cells degrade and recycle unwanted or damaged components. This keeps cells functional, prevents toxic buildup, and provides energy during nutrient shortages.

It works through autophagosomes, double-membrane vesicles that engulf waste and fuse with lysosomes to break it down.

Autophagy and Ageing

  • Decline With Age: Reduced autophagy contributes to protein clumping, mitochondrial dysfunction, and inflammation.
  • Neurodegeneration: Impaired autophagy is linked to Alzheimer’s, Parkinson’s, Huntington’s.
  • Longevity: Enhanced autophagy is associated with longer lifespan in animals.
  • Hallmarks Impacted:
  • Proteostasis: Clears misfolded proteins.
  • Mitochondria: Removes defective mitochondria (mitophagy).
  • Nutrient Sensing: Activated by low insulin/mTOR signalling.
  • Cellular Senescence: Prevents accumulation of dysfunctional cells.

Biological Functions & Mechanisms

  1. Protein Quality Control: Breaks down damaged or misfolded proteins.
  2. Mitophagy: Clears damaged mitochondria, preserving energy function.
  3. Pathogen Defence: Destroys bacteria and viruses inside cells.
  4. Nutrient Recycling: Provides energy during fasting or starvation.
  5. Cancer Prevention: Removes potentially tumour-promoting damaged components.

Autophagy & Longevity Interventions

Lifestyle Activators

  • Fasting & Caloric Restriction: Strongest natural triggers.
  • Exercise: Boosts autophagy in muscle and brain.
  • Sleep: Supports autophagic repair cycles.

Nutritional & Supplement Activators

  • Spermidine: Directly induces autophagy, studied as a longevity supplement.
  • Resveratrol: Activates SIRT1, indirectly enhancing autophagy.
  • Curcumin & Quercetin: Polyphenols with autophagy-promoting effects.
  • Green Tea Catechins (EGCG): Support autophagy pathways.

Pharmaceutical Activators

  • Rapamycin: mTOR inhibitor, strong autophagy inducer.
  • Metformin: Indirectly enhances autophagy via AMPK activation.

Discovery and Research History

  • 1960s: Term “autophagy” introduced by Christian de Duve (Nobel laureate).
  • 1990s–2000s: Molecular mechanisms discovered (Yoshinori Ohsumi’s work).
  • 2016: Ohsumi awarded Nobel Prize in Medicine for autophagy research.
  • Today: Considered a pillar of longevity biology and therapeutic target.

Safety and Considerations

  • Too Little: Associated with ageing, disease, and immune dysfunction.
  • Too Much: Excessive autophagy may cause muscle wasting or support cancer survival in some contexts.
  • Balanced Regulation: Pulsed activation (fasting, supplements) may be most beneficial.

FAQs

What triggers autophagy naturally?
Fasting, exercise, calorie restriction, and sleep cycles.

Does autophagy extend lifespan?
Yes in animals; in humans, it is strongly correlated with healthier ageing.

What’s the difference between autophagy and mitophagy?
Mitophagy is a subtype of autophagy that specifically removes damaged mitochondria.

Can you measure autophagy?
In humans, it’s difficult — researchers use biomarkers, not direct measures.

Glossary

  • Autophagosome: Vesicle that engulfs damaged cellular components.
  • Lysosome: Organelle that digests waste materials.
  • mTOR: Nutrient-sensing pathway that inhibits autophagy when active.
  • AMPK: Energy sensor that promotes autophagy.
  • Mitophagy: Selective clearance of damaged mitochondria.

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