Longevity & AgingNew Autophagy Activator AA-20 Extends Worm Lifespan Without Blocking mTOR
Researchers identified AA-20, a small-molecule autophagy activator discovered through a million-compound screen, that clears lipid droplets and protein aggregates in human cells and C. elegans. Unlike rapamycin and most known autophagy inducers, AA-20 activates autophagy without inhibiting mTORC1—instead acting through the transcription factor HLH-30/TFEB. In nematodes, AA-20 reduced polyglutamine aggregation, improved fitness markers, and significantly extended lifespan. These effects were abolished in autophagy-deficient mutants, confirming autophagy dependence. The compound represents a potentially cleaner therapeutic avenue for age-related proteinopathies and lipid storage disorders, sidestepping the immunosuppressive side effects of mTOR inhibition.
