A Recycling Mechanism that Helps Cells Fight Aging

(EPFL, July 01, 2025)

Researchers have found activating the LySR pathway in worms extends their lives by 60%, opening new research avenues for increasing human healthspan and fighting neurodegenerative diseases. Dr. Johan Auwerx's team at EPFL, alongside Fudan University, Amsterdam UMC, and Baylor College of Medicine, discovered the Lysosomal Surveillance Response (LySR) pathway in worms (Caenorhabditis elegans). This pathway boosts cells' waste-clearing abilities, including the removal of toxic proteins linked to neurodegenerative diseases, offering a potential mechanism to enhance cellular health and promote healthy aging. The team's research showed that disabling waste-disposal genes, particularly those for vacuolar H+-ATPase subunits crucial for lysosome function, unexpectedly activates the LySR pathway. They tracked the worms' capacity to eliminate protein buildup, lifespan, resistance to aging and disease, and tested LySR activation in worm models of Alzheimer’s and Huntington’s disease. These findings pave the way for developing new therapies targeting the LySR pathway, aiming to treat or prevent neurodegenerative diseases by improving cellular waste management, thereby extending healthspan and disease resistance.