Aging isn’t just a dimmer switch; it’s a logistics failure. In
, Doug Henze, Tony Wyss-Coray, and I show how mRNA “gets stuck” in aging microglia, causing degradation of their spatial context: https://nature.com/articles/s43587-026-01089-z
Mechanistically, the accumulation of sphingolipids and cholesterol in lysosomes drives a buildup of protein aggregates, involving lipid-driven dysfunction of the ESCRT machinery66. Abnormal lysosomal lipid remodelling also impairs its degradation capacity by disrupting lysosomal fusion with endosomes and autophagosome