Longevity & AgingRNA Structures Called rG4 Accelerate Cellular Aging by Stalling Protein-Making Machinery
Researchers found that RNA G-quadruplex (rG4) structures—non-canonical RNA folds that form in guanine-rich regions—increase significantly in senescent human cells and aged mouse tissues. Using ribosome profiling and G4 immunoprecipitation sequencing, the team showed these structures physically stall ribosomes during translation, reducing protein production efficiency and worsening cellular senescence. The RNA helicase DHX9, which normally unwinds rG4 structures, is markedly reduced in senescent cells, allowing rG4 to accumulate unchecked. Artificially stabilizing rG4 structures accelerated senescence, while the DHX9-rG4-ribosome pausing axis was confirmed in aged mouse fibroblasts and tissues, pointing to a conserved aging mechanism with potential therapeutic relevance.
