{"id":"0d5885e5-0120-5494-98ab-14344813fb70","stable_key":"ff370329-68a3-573d-96ee-597de78a3967:api-nmn-sirt3-benefit-attenuated","predicate":"decreases_in_recorded_comparison","statement":"Sirt3 deletion partially attenuated the structural and functional benefits of NMN plus apigenin.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"3b3567c3-32fa-5ddc-98e9-df3422eb692a","mechanism_event_label":"Sirt3 deletion partially attenuated the structural and functional benefits of NMN plus apigenin.","subject":{"id":"6d70addf-e302-5605-9c6a-02358209c876","slug":"nmn-apigenin-combination-2026","display_name":"NMN plus apigenin preparation in the 2026 musculoskeletal study","entity_type_key":"chemical_species"},"object":{"id":"a00a8eaa-b50a-5b1d-831c-d38da40425b4","slug":"api-nmn-aged-musculoskeletal-outcomes","display_name":"Musculoskeletal outcomes in aged NMN/apigenin-treated mice","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"3b3567c3-32fa-5ddc-98e9-df3422eb692a","stable_key":"ff370329-68a3-573d-96ee-597de78a3967:api-nmn-sirt3-benefit-attenuated-event","event_type":"experimental_observation","label":"Sirt3 deletion partially attenuated the structural and functional benefits of NMN plus apigenin.","description":"### api-nmn-sirt3-benefit-attenuated\n\nSirt3 deletion partially attenuated the structural and functional benefits of NMN plus apigenin.\nPartial attenuation supports a contributing requirement; it is not complete elimination or direct apigenin binding to SIRT3.\nModel and exposure: Aged-mouse genotype comparison.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Double-Pronged NAD Preservation: Delaying Cellular Senescence and Initiating Musculoskeletal Regeneration. | 2026 | https://pubmed.ncbi.nlm.nih.gov/41944220/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13054677/ | https://doi.org/10.1111/acel.70468 | Access: Primary main-text Results and figure descriptions reviewed. Detailed supporting Methods/supplements inaccessible; exact doses and preparation details not independently extracted.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"6d70addf-e302-5605-9c6a-02358209c876","slug":"nmn-apigenin-combination-2026","display_name":"NMN plus apigenin preparation in the 2026 musculoskeletal study","entity_type_key":"chemical_species"},"role":"tested factor","stoichiometry":null,"state_label":"Combined preparation in Sirt3-knockout mice","sequence_order":0,"notes":""},{"entity":{"id":"a00a8eaa-b50a-5b1d-831c-d38da40425b4","slug":"api-nmn-aged-musculoskeletal-outcomes","display_name":"Musculoskeletal outcomes in aged NMN/apigenin-treated mice","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"decrease","sequence_order":1,"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 main-text Results and figure descriptions reviewed. Detailed supporting Methods/supplements inaccessible; exact doses and preparation details not independently extracted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"co-administered","comparator":"Combined-preparation response in wild-type mice","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"apigenin","display_name":"Apigenin","entity_type_key":"small_molecule"}},{"dimension":"experimental_condition","value_text":"genetically absent","comparator":"Combined-preparation response in wild-type mice","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"mouse-sirt3","display_name":"Mouse mitochondrial sirtuin 3 / Sirt3","entity_type_key":"protein"}},{"dimension":"experimental_condition","value_text":"co-administered","comparator":"Combined-preparation response in wild-type mice","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"nmn","display_name":"NMN","entity_type_key":"small_molecule"}},{"dimension":"experimental_condition","value_text":"Combined preparation in Sirt3-knockout mice","comparator":"Combined-preparation response in wild-type mice","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"nmn-apigenin-combination-2026","display_name":"NMN plus apigenin preparation in the 2026 musculoskeletal study","entity_type_key":"chemical_species"}},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"Combined preparation in Sirt3-knockout mice\", \"comparator\": \"Combined-preparation response in wild-type mice\", \"endpoint\": \"Sirt3 deletion partially attenuated the structural and functional benefits of NMN plus apigenin.\", \"effect_direction\": \"decrease\", \"combination\": \"joint\", \"conditions\": [{\"entity_slug\": \"nmn-apigenin-combination-2026\", \"state\": \"Combined preparation in Sirt3-knockout mice\"}, {\"entity_slug\": \"nmn\", \"state\": \"co-administered\"}, {\"entity_slug\": \"apigenin\", \"state\": \"co-administered\"}, {\"entity_slug\": \"mouse-sirt3\", \"state\": \"genetically absent\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; recorded from source.","entity":null},{"dimension":"experimental_model","value_text":"Aged-mouse genotype comparison.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Recorded from source with stated access limits; ungraded, not independent replication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Apigenin collection; exact intervention and molecular form govern interpretation.","comparator":null,"unit":null,"notes":"","entity":{"slug":"apigenin","display_name":"Apigenin","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Sirt3 deletion partially attenuated the structural and functional benefits of NMN plus apigenin.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Double-Pronged NAD Preservation: Delaying Cellular Senescence and Initiating Musculoskeletal Regeneration. | https://pubmed.ncbi.nlm.nih.gov/41944220/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13054677/ | https://doi.org/10.1111/acel.70468","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference api-nmn-sirt3-benefit-attenuated; Partial attenuation supports a contributing requirement; it is not complete elimination or direct apigenin binding to SIRT3.","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":"aeab6b53-dc30-5340-af40-464758a43fb9","evidence_kind":"source_excerpt","locator":"Lines 564-570","start_line":564,"end_line":570,"excerpt":"### api-nmn-sirt3-benefit-attenuated\n\nSirt3 deletion partially attenuated the structural and functional benefits of NMN plus apigenin.\nPartial attenuation supports a contributing requirement; it is not complete elimination or direct apigenin binding to SIRT3.\nModel and exposure: Aged-mouse genotype comparison.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: Double-Pronged NAD Preservation: Delaying Cellular Senescence and Initiating Musculoskeletal Regeneration. | 2026 | https://pubmed.ncbi.nlm.nih.gov/41944220/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13054677/ | https://doi.org/10.1111/acel.70468 | Access: Primary main-text Results and figure descriptions reviewed. Detailed supporting Methods/supplements inaccessible; exact doses and preparation details not independently extracted.","model_system":"Aged-mouse genotype comparison.","directness":"reported_statement","verification_status":"source_recorded","notes":"Original paraphrase in the retained reviewed reference, not a verbatim primary-paper quotation. Access level is explicit.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"54eac90b-add1-5f56-9036-d900307c5697","stable_key":"import-ff370329-68a3-573d-96ee-597de78a3967","title":"Apigenin: detailed mechanisms of action (reviewed 10 October 2026)","document_type":"imported_text","citation_label":"AI-assisted original curation of primary studies; claim-local access and experimental limitations stated. Includes original-draft correction history. No independent replication claimed.","file_path":"","sha256":"ede6e5c6b91d66b66844f2ff667a7f8303d9ac1281f15dc09db703f7de4da942","revision_id":"b41a39a2-0197-549c-97a5-1765e6696931","review_status":"source_recorded","notes":""}}],"relations":[{"id":"d560466a-ceaa-5d27-9428-677cbb5b0de5","relation_type":"limits_scope_of","notes":"NAD supply can remain responsive while a downstream dependency weakens outcomes.","source_claim_id":"e0ddd315-8276-5d22-9cda-3a830c63d7e9","source_claim_key":"ff370329-68a3-573d-96ee-597de78a3967:api-nmn-sirt3-nad-retained","source_statement":"The NMN/apigenin-associated blood NAD+ and NAD+/NADH increases persisted in Sirt3-knockout mice.","target_claim_id":"0d5885e5-0120-5494-98ab-14344813fb70","target_claim_key":"ff370329-68a3-573d-96ee-597de78a3967:api-nmn-sirt3-benefit-attenuated","target_statement":"Sirt3 deletion partially attenuated the structural and functional benefits of NMN plus apigenin."}],"conflicts":[],"corrections":[],"research":null}