Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans.

ABSTRACT: Ribosome biogenesis is initiated by RNA polymerase I (Pol I)-mediated synthesis of pre-ribosomal RNA (pre-rRNA). Pol I activity was previously linked to longevity, but the underlying mechanisms were not studied beyond effects on nucleolar structure and protein translation. Here we use multi-omics and functional tests to show that curtailment of Pol I activity remodels the lipidome and preserves mitochondrial function to promote longevity in Caenorhabditis elegans. Reduced pre-rRNA synthesis improves energy homeostasis and metabolic plasticity also in human primary cells. Conversely, the enhancement of pre-rRNA synthesis boosts growth and neuromuscular performance of young nematodes at the cost of accelerated metabolic decline, mitochondrial stress and premature aging. Moreover, restriction

SUBMITTER: Sharifi S 

PROVIDER: S-EPMC10894287 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature