Researchers at Baylor College of Medicine discovered that lysosomal metabolic signals extend lifespan not just in one organism but across multiple generations in C. elegans. Activating lysosomal lipid breakdown (via LIPL-4 overexpression), boosting lysosomal AMPK, or reducing mTOR signaling all increased expression of histone variant H3.3 (HIS-71) in the intestine and elevated H3K79 methylation genome-wide. Intestinal HIS-71 protein was then physically transported to the germline via vitellogenin-mediated yolk transport, where a germline-specific H3K79 methyltransferase (DOT-1.3) wrote heritable epigenetic marks. These changes propagated longevity benefits to descendants for up to three generations, establishing a soma-to-germline epigenetic communication axis.
