Autophagy Study Suggests New Strategy for Treating Age-Related Neurodegenerative Diseases

Scientists from Brown University say they have demonstrated a novel method for stimulating autophagy. In a study (“ Nuclear Export Inhibition Enhances HLH-30/TFEB Activity, Autophagy, and Lifespan ”), published in  Cell Reports , the team shows that the approach increased the lifespans of worms and flies, and experiments in human cells hint that the strategy could be useful in future treatments for Alzheimer's disease, amyotrophic lateral sclerosis ( ALS), and other age-related neurodegenerative conditions.

“Transcriptional modulation of the process of autophagy involves the transcription factor HLH-30/TFEB. In order to systematically determine the regulatory network of HLH-30/TFEB, we performed a genome-wide RNAi [RNA interference] screen in  C. elegans  and found that silencing the nuclear export protein XPO-1/XPO1 enhances autophagy by significantly enriching HLH-30 in the nucleus, which is accompanied by proteostatic benefits and improved longevity. Lifespan extension via  xpo-1  silencing requires HLH-30 and autophagy, overlapping mechanistically with several established longevity models. Selective XPO1 ...