{"id":"d12dae9f-487d-50dd-9d1d-b256422414a2","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-late-life-tradeoff","predicate":"has_mixed_effects_on","statement":"Starting 67% isoleucine restriction at twenty months improved selected metabolic/frailty measures but reduced grip strength in both sexes and produced mixed sex-dependent cardiac effects.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2e7f08ef-8a45-5e77-b4a8-e205176a3722","mechanism_event_label":"A diet can improve some endpoints while worsening others.","subject":{"id":"59da00d5-9277-5068-9c49-775200ebb582","slug":"mouse-low-isoleucine-diet","display_name":"Experimentally reduced-isoleucine mouse diet","entity_type_key":"cellular_process"},"object":{"id":"fce10116-fcbb-5ad6-832a-c97fb158ae59","slug":"mouse-late-life-isoleucine-function","display_name":"Functional outcomes of late-life isoleucine restriction","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2e7f08ef-8a45-5e77-b4a8-e205176a3722","stable_key":"09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2:isoleucine-late-life-tradeoff-event","event_type":"observed_relationship","label":"A diet can improve some endpoints while worsening others.","description":"Starting 67% isoleucine restriction at twenty months improved selected metabolic/frailty measures but reduced grip strength in both sexes and produced mixed sex-dependent cardiac effects.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"59da00d5-9277-5068-9c49-775200ebb582","slug":"mouse-low-isoleucine-diet","display_name":"Experimentally reduced-isoleucine mouse diet","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"fce10116-fcbb-5ad6-832a-c97fb158ae59","slug":"mouse-late-life-isoleucine-function","display_name":"Functional outcomes of late-life isoleucine restriction","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c85b327e-f132-5d9a-8e4b-c2976fcc0373","slug":"isoleucine","display_name":"L-Isoleucine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Aged male and female C57BL/6J.Nia mice.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not evidence that severe restriction is desirable in older humans; differs from the six-month-start longevity experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"isoleucine","display_name":"L-Isoleucine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A diet can improve some endpoints while worsening others.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39604703/ · DOI 10.1038/s43587-024-00744-7","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"a17caf6c-2355-5f2b-88a9-2b9642e34cce","evidence_kind":"source_excerpt","locator":"Lines 426-432","start_line":426,"end_line":432,"excerpt":"## isoleucine-late-life-tradeoff\nA diet can improve some endpoints while worsening others.\nStarting 67% isoleucine restriction at twenty months improved selected metabolic/frailty measures but reduced grip strength in both sexes and produced mixed sex-dependent cardiac effects.\nModel: Aged male and female C57BL/6J.Nia mice.\nLimitations: Not evidence that severe restriction is desirable in older humans; differs from the six-month-start longevity experiment.\nEvidence access: Primary abstract\nLate-life protein or isoleucine restriction impacts physiological and molecular signatures of aging. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39604703/ · DOI 10.1038/s43587-024-00744-7","model_system":"Aged male and female C57BL/6J.Nia mice.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4b00f118-00fd-5cef-be97-13125eb958e9","stable_key":"import-09b23d0d-35e2-51ff-b1aa-b4f9227e4fa2","title":"L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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