Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease, and approximately 90% of cases are caused by progerin. Progerin is toxic and causes diverse abnormalities. More and more studies show that progerin is also detected in physiological aging and chronic kidney disease (CKD). Thus, targeting progerin clearance shows powerful potential for the treatment of HGPS, CKD and aging-related diseases. Now, Zhang group from Peking University and Kunming University of Science and Technology, reports that activating lysosome biogenesis can promote progerin clearance and alleviate cellular senescence in HGPS. They identify lysosome defects as a prevalent feature in HGPS, which impairs progerin clearance, and reveal that activating lysosome biogenesis can counteract lysosome defects and accelerate progerin clearance and mitigate DNA damage, cell cycle arrest, low proliferation ability and senescence-associated secretory phenotype (SASP) in HGPS cells. The findings highlight the vital role of lysosomes in progerin clearance, and uncover the potential of targeting lysosome biogenesis in anti-senescence.

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