{"id":"9ac1c759-4dd5-5f7b-a5e4-9bffc485a135","stable_key":"220adaab-10d8-5c4e-a3f5-a48700ea794d:agmatine-sulfate-bacterial-metformin","predicate":"requires_in_model","statement":"Metformin no longer extended C. elegans lifespan when worms ate E. coli lacking both agmatine-production genes adiA and speA.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d8fc3eb0-8ea9-5fdb-a74d-53aecd96af13","mechanism_event_label":"A drug response depended on the microbes in a specific experimental system.","subject":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"object":{"id":"2ad944ae-0afc-53d8-a837-0cc7f411f1cd","slug":"ecoli-agmatine-production-for-worm-lifespan","display_name":"E. coli agmatine production in the metformin worm-lifespan model","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"d8fc3eb0-8ea9-5fdb-a74d-53aecd96af13","stable_key":"220adaab-10d8-5c4e-a3f5-a48700ea794d:agmatine-sulfate-bacterial-metformin-event","event_type":"observed_relationship","label":"A drug response depended on the microbes in a specific experimental system.","description":"Metformin no longer extended C. elegans lifespan when worms ate E. coli lacking both agmatine-production genes adiA and speA.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"519971b1-5aef-5ad7-8022-840144855cd0","slug":"metformin","display_name":"Metformin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2ad944ae-0afc-53d8-a837-0cc7f411f1cd","slug":"ecoli-agmatine-production-for-worm-lifespan","display_name":"E. coli agmatine production in the metformin worm-lifespan model","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ae2dddf4-ce04-57e3-8a06-7ed9fdc24554","slug":"agmatine-sulfate","display_name":"Agmatine Sulfate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"e2f83eb4-99ed-5050-87d3-3e4701d05c1a","slug":"agmatine","display_name":"Agmatine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text; Figure 4I","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Worm lifespan with defined E. coli deletion mutants.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"No human lifespan extension or agmatine-sulfate/metformin combination efficacy is established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"agmatine-sulfate","display_name":"Agmatine Sulfate","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A drug response depended on the microbes in a specific experimental system.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Host-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31474368/ · DOI 10.1016/j.cell.2019.08.003","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"bd202fac-2b17-5d04-9931-fc0f0db092fc","evidence_kind":"source_excerpt","locator":"Lines 412-418","start_line":412,"end_line":418,"excerpt":"## agmatine-sulfate-bacterial-metformin\nA drug response depended on the microbes in a specific experimental system.\nMetformin no longer extended C. elegans lifespan when worms ate E. coli lacking both agmatine-production genes adiA and speA.\nModel: Worm lifespan with defined E. coli deletion mutants.\nLimitations: No human lifespan extension or agmatine-sulfate/metformin combination efficacy is established.\nEvidence access: Primary full text; Figure 4I\nHost-Microbe-Drug-Nutrient Screen Identifies Bacterial Effectors of Metformin Therapy. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31474368/ · DOI 10.1016/j.cell.2019.08.003","model_system":"Worm lifespan with defined E. coli deletion mutants.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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