EverspanAutophagy: The Cell's Recycling System
Macroautophagy is the process by which cells engulf and digest their own damaged components – misfolded proteins, dysfunctional organelles, and pathogens. It is one of the most important longevity mechanisms, progressively impaired by mTOR hyperactivation with age. Click any step below to explore the molecular biology and which interventions act at that stage.
MACROAUTOPHAGY – 5 STEPS · Click a step to expand details
Why autophagy declines with age
mTOR hyperactivation. Chronic nutrient abundance and reduced insulin sensitivity cause persistent mTORC1 activation in aged cells, constitutively suppressing ULK1 and blocking autophagy initiation.
Beclin-1 decline. Beclin-1 protein levels fall markedly in aged tissues. The anti-apoptotic proteins Bcl-2 and Bcl-xL increasingly sequester Beclin-1 away from the PI3K complex, impairing phagophore nucleation.
Reduced ATG protein expression. Global downregulation of ATG5, ATG7, ATG12, and LC3 transcription in aged tissues results in fewer and smaller autophagosomes. Lysosomal cathepsin activity also declines, creating a degradation bottleneck.
Key autophagy-activating interventions