Modulation of the RNAse P/MRP complex and mitochondrial ribosome enhances cytosolic ribosome coordination and sustains longevity

Aging is accompanied by declining protein synthesis and ribosome abundance, yet reduced translation can extend lifespan. Whether the age-associated decline is adaptive or reflects a pathological failure remains unclear. Here, we show that a breakdown in the coordination of ribosome biogenesis and assembly drives shortened lifespan. We identify the C. elegans ncl-1/BRAT tumor suppressor as a key coordinator of ribogenesis as well as cytosolic and mitochondrial ribosome production, whose loss leads to premature aging and proteostasis collapse. Importantly, we demonstrate that restoring cytosolic ribosomal homeostasis downstream of the nucleolus, by tamping down ribogenesis factor M/RNAse P and mitochondrial ribosomes, is sufficient to rescue cytosolic ribosomal coordination, proteostasis and longevity. Our findings identify age-associated ribosome dysfunction as a qualitative failure of ribosomal biogenesis, and show that restoring ribosomal homeostasis is sufficient to improve proteostasis and extend lifespan.