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
- Protein Quality Control: Breaks down damaged or misfolded proteins.
- Mitophagy: Clears damaged mitochondria, preserving energy function.
- Pathogen Defence: Destroys bacteria and viruses inside cells.
- Nutrient Recycling: Provides energy during fasting or starvation.
- 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.
