PR001490 (Project)

Id Namespace:

UCSD Metabolomics Workbench

Identifier Namespace (Entity type)

Dcc Asset:

MW submission packet 20250922.zip

Processed File (Entity type)

Dcc:

Metabolomics

DCC (Entity type)

Persistent Id:http://dx.doi.org/10.21228/M84D89

Description:Ribosome biogenesis is an anabolic process driven by RNA polymerase I (Pol I)-mediated synthesis of pre-ribosomal RNA (pre-rRNA). While Pol I activity was previously linked to longevity, the underlying mechanisms were not studied beyond effects on protein translation and downstream proteostasis. Here we used multi-omics and functional tests to show that curtailment of Pol I activity preserves mitochondrial function and lowers ATP expenditure, thereby promoting longevity in Caenorhabditis elegans. Reduced pre-rRNA synthesis also improved longevity and energy homeostasis in Drosophila melanogaster and human cells, respectively. Conversely, the enhancement of pre-rRNA synthesis boosted growth and neuromuscular performance of young nematodes at the cost of accelerated metabolic decline, mitochondrial stress and premature aging. Moreover, restriction of Pol I activity extended lifespan more potently than translational repression, and retained its geroprotective effects when initiated late in life, showcasing moderation of Pol I activity as an effective longevity treatment not limited by aging.

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	Label	Description
	PPR00001 Project (Entity type)	Metabolomics
	SU002411 Subject (Entity type)	A subject from Metabolomics produced as part of the PR001490 project
	SU002413 Subject (Entity type)	A subject from Metabolomics produced as part of the PR001490 project
	SU002412 Subject (Entity type)	A subject from Metabolomics produced as part of the PR001490 project
	SA229325 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001490 project
	SA229167 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001490 project
	SA229423 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001490 project
	SA229313 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001490 project
	SA229163 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001490 project
	SA229138 Biosample (Entity type)	A biosample from Metabolomics produced as part of the PR001490 project