Longevity & AgingSenescent Cells Evade Iron-Driven Death Via Faulty Lysosomes
Senescent cells accumulate iron yet resist ferroptosis, a form of iron-dependent cell death. Researchers discovered that lysosomal alkalinization — a hallmark of cellular senescence — traps ferrous iron inside lysosomes, preventing it from driving lipid peroxidation in the cytoplasm and membranes. Restoring lysosomal acidity with EN6, a V-ATPase activator, re-sensitized senescent cells to ferroptosis. The same mechanism was found in ferroptosis-resistant pancreatic cancer cells. EN6 treatment suppressed pancreatic cancer growth in both xenograft and Kras mutant mouse models, suggesting lysosomal re-acidification as a dual strategy against senescence-driven aging disease and therapy-resistant cancers.
