Scientists in China report that repairing defects in lysosomes—the cell’s waste‑disposal hubs—accelerated clearance of progerin in patient cells and reduced markers of cellular aging, pointing to a potential therapeutic target for Hutchinson‑Gilford progeria syndrome.
Hutchinson‑Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder that causes children to age rapidly. Hallmark features include loss of subcutaneous fat, hair loss, thin and wrinkled skin, cardiovascular disease from hardening of the arteries, joint problems, and insulin resistance, while cognition is typically preserved. (mayoclinic.org)
Roughly 90% of HGPS cases arise from LMNA gene mutations that produce a toxic lamin A variant called progerin, which disrupts nuclear structure and drives cellular damage. (dx.doi.org)
In a paper published September 5, 2025, in Science China Life Sciences, a team led by Professor Chuanmao Zhang of Peking University and Kunming University of Science and Technology reports that lysosomes play a central role in clearing progerin through the autophagy‑lysosome pathway—and that defects in this system contribute to its buildup in HGPS cells. (dx.doi.org)
Using imaging, live‑cell observation, and biochemical analyses, the researchers traced progerin’s movement from the nuclear envelope into the cytoplasm via nuclear envelope budding, where it is normally degraded by autophagy. They found that HGPS cells show lysosomal dysfunction. According to Science China Press’s summary of the work, RNA sequencing of primary cells from two HGPS patients revealed reduced activity of lysosome‑related genes, findings supported by additional molecular assays. (sciencedaily.com)
To restore the pathway, the team boosted lysosome biogenesis by activating protein kinase C (PKC) with phorbol 12‑myristate 13‑acetate (PMA) or by inhibiting mTORC1 with Torin 1. Both interventions enhanced lysosomal function, accelerated progerin removal, and mitigated cellular aging markers, including DNA damage, cell‑cycle arrest, low proliferation, and elements of the senescence‑associated secretory phenotype. (dx.doi.org)
The authors say these results position lysosomes as a promising therapeutic target in HGPS. Science China Press further notes that small amounts of progerin have been detected in normal aging and in the arteries of people with chronic kidney disease—contexts that could broaden the relevance of lysosome‑targeted strategies—though the new findings are preclinical and limited to cell models. (sciencedaily.com)
