The dire side of autophagy in aging: Lessons from C. elegans

摘要

Autophagy is an essential cellular process that eliminates cellular debris, dysfunctional organelles and misfolded proteins thereby maintaining cellular metabolism and homeostasis. Functional autophagy is generally thought to counteract aging and is crucial for the prolonged lifespan and health of an animal. Whereas this statement is true for young animals, we have recently shown that autophagy becomes dysfunctional in post-reproductive C. elegans contributing to aging and neurodegeneration. Downregulation of autophagy nucleation in post-reproductive nematodes causes a lifespan extension and preservation of neuronal integrity putting the generally accepted view of the role of autophagy in aging into question. Here we discuss specific cellular degradation programs in young and old animals and speculate on molecular mechanisms that might explain this unexpected role of autophagy in aged animals.