{ "completed": true, "status": "completed_original_source_reconciliation", "provider_mode": "Consensus Pro signed-in browser; observed output and citation link mappings", "queries": [ "https://consensus.app/search/intermittent-rapamycin-effects-aging/npYAPuOsTsiiYWqvevUzQw/" ], "query_record_note": "Exact provider question/response retained privately in its retrieval receipt.", "primary_comparison_count": 10, "primary_comparisons": [ { "pmid": "41985884", "doi": "10.1002/jcsm.70274", "source_type": "primary study report", "study_group": "ACTRN12624000790549", "access_depth": "full_text_partial", "consensus_aspect": "Functional primary result versus universal no-effect language", "result_comparison": "Consensus correctly gives the chair-stand estimate−2.13,P.089 and per-protocol negative contrast. Its categorical headline that intermittent rapamycin does not improve function exceeds this 40-person 13-week exercise regimen. The original ITTresult is negative-direction nonsignificance, with prespecified sensitivity attenuation; neither definitive equivalence nor every-dose ineffectiveness follows.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/41985884/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-0-10-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\41985884-s1-p0-8-9-10-11-14-15-16-17.json", "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\41985884-s2-p3-4-5-7-9-10-13-14-16.json" ] }, { "pmid": "41985884", "doi": "10.1002/jcsm.70274", "source_type": "primary study report", "study_group": "ACTRN12624000790549", "access_depth": "full_text_partial", "consensus_aspect": "Adverse-event uncertainty and pneumonia attribution", "result_comparison": "Consensus says event burden was elevated and calls pneumonia drug-related. Original Results give 99 versus 63 events,IRR1.57,95%CI0.86–2.87,P.14. The single hospitalized pneumonia after one dose was possibly related, with causal contribution not excluded. We preserve the concern without turning an imprecise count or possible attribution into proven increased infection risk.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/41985884/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-0-10-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\41985884-s1-p0-8-9-10-11-14-15-16-17.json", "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\41985884-s2-p3-4-5-7-9-10-13-14-16.json" ] }, { "pmid": "40188830", "doi": "10.18632/aging.206235", "source_type": "primary study report", "study_group": "NCT04488601", "access_depth": "full_text_partial", "consensus_aspect": "Primary hierarchy, functional outcomes and female subset", "result_comparison": "Consensus accurately identifies visceral-fat primary null and female leanmass/pain signals. Original Methods state SF36/WOMACwere not specific study endpoints. Actual Results analyzed 114 completers excluding 11 discontinuers;only eight women received 10 mg. WOMACwas null and emotional wellbeing improved within placebo too. Selected composition/survey findings are retained with small-subgroup, multiplicity and between-versus-within-arm limits.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/40188830/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-10-20-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\40188830-s1-p0-1-3-5-7-9-10-13.json", "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\40188830-s3-p0-1-2-3-9-11-12.json" ] }, { "pmid": "40188830", "doi": "10.18632/aging.206235", "source_type": "primary study report", "study_group": "NCT04488601", "access_depth": "full_text_partial", "consensus_aspect": "Bioavailability measurement versus exact dose equivalence", "result_comparison": "Consensus translates compounded 5/10 mg into true circulating 1.65/3.3 mg weekly equivalents. Original PEARL says a separate assessment found approximately one-third the 24-hour blood concentration of commercial drug. A single concentration comparison is not verified AUC or clinical-effect bioequivalence. Nominal dose and actual exposure remain distinct; exact interchangeable milligram claims are not carried.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/40188830/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-10-20-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\40188830-s1-p0-1-3-5-7-9-10-13.json", "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\40188830-s3-p0-1-2-3-9-11-12.json" ] }, { "pmid": "29408453", "doi": "10.1016/j.exger.2017.12.026", "source_type": "primary study report", "study_group": "NCT02874924", "access_depth": "full_text_partial", "consensus_aspect": "Daily pilot duration, denominators and concentration", "result_comparison": "Consensus treats Kraig as eight-week daily dosing and cites 6.1–8.2 ng/m L. Actual Methods include an initial eight-person planned four-month phase and 20-person eight-week phase;28 enrolled and 25≥8 weekcompleters. The cited concentrations are phase 1 maxima, while the Results report wider individual levels. Daily/short pilot function null does not become the registered 12–104 week intermittent trial or universal safety result.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/29408453/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-0-10-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\29408453-s1-p0-1-2-3-4-10.json", "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\29408453-s2-p0-1-3-5-6-8-9-10.json" ] }, { "pmid": "40704394", "doi": "10.1111/acel.70183", "source_type": "primary study report", "study_group": "PMID40704394", "access_depth": "abstract_metadata", "consensus_aspect": "Mouse exercise-adaptation direction and clinical transfer", "result_comparison": "Consensus cites Elliehausen 2025 for the assertion that intermittentm TORinhibition impedes muscular adaptations. The selected original explicitly found preserved exercise capacity, grip and hypertrophy in adult female mice under weekly/frequent schedules, while glucose tolerance worsened. We retain both findings and reject the wrong-direction transfer to human training impairment. Acute human 19188252 protein-synthesis suppression is a different original and endpoint.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/40704394/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-10-20-10000.json" ], "body_receipts": [] }, { "pmid": "33977284", "doi": "10.1016/S2666-7568(21)00062-3", "source_type": "primary study report", "study_group": "PMID33977284", "access_depth": "abstract_metadata", "consensus_aspect": "Contradictory immune clinical evidence", "result_comparison": "Consensus summarizes vaccine/infection benefits using review-mediated citations. Our selected originals preserve those positives and also the later RTB101 phase IIIclinical-illness null despite antiviral gene upregulation. Phase 2 bfirst-comparison failure and pooled laboratory-infection positive remain distinct. Immune effects cannot be treated as uniformly positive or as weeklyrapamycin physical-function/survival proof.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/33977284/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-46-49-10000.json" ], "body_receipts": [] }, { "pmid": "19587680", "doi": "10.1038/nature08221", "source_type": "primary study report", "study_group": "PMID19587680", "access_depth": "abstract_metadata", "consensus_aspect": "Animal longevity validity and translation", "result_comparison": "Consensus correctly acknowledges preclinical longevity/function. Actual late-life heterogeneous-mouse original extends survival across sites and both sexes; further originals map dose, sex and healthspan-survival dissociations. These are real restricted causal results. Neither a human functional null erases them nor do they establish human intermittent physical benefit.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/19587680/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-10-20-10000.json" ], "body_receipts": [] }, { "pmid": "41985884", "doi": "10.1002/jcsm.70274", "source_type": "primary study report", "study_group": "ACTRN12624000790549", "access_depth": "full_text_partial", "consensus_aspect": "Provider washout requirement is unsupported", "result_comparison": "Consensus claims 3–6 week washouts are required to clear a 62-hour half-life and prevent anabolic interference. This is not an established treatment schedule from the original. RAPA-EX tested weekly dosing around exercise; its results motivate prospective timing/dose experiments without proving a required washout duration. No dosing advice or unsupported requirement is copied into the review.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/41985884/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-0-10-10000.json" ], "body_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\41985884-s1-p0-8-9-10-11-14-15-16-17.json", "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\body-presentation-receipts\\41985884-s2-p3-4-5-7-9-10-13-14-16.json" ] }, { "pmid": "38956196", "doi": "10.1038/s41591-024-03096-2", "source_type": "primary study report", "study_group": "NCT04313634", "access_depth": "abstract_metadata", "consensus_aspect": "Provider coverage is not a primary evidence count", "result_comparison": "Consensus matrices include review/protocol-mediated counts across regimens. Our independently selected senolytic originals show different pathways and endpoint limits: postmenopausal primary CTxnull, exploratory subset/earlymarkers, and controlled IPFfunctional null. Provider paper counts are discovery indicators, not examined originals, independent studies or evidence that senolytics reproduce a proven rapamycin benefit.", "original_source": "https://pubmed.ncbi.nlm.nih.gov/38956196/", "source_examination_receipts": [ "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\examinations\\original-0-10-10000.json" ], "body_receipts": [] } ], "grade_changed": false, "grade_change_note": "Source-based adjudication; no independent blinded regrade claimed.", "raw_receipts": [ { "path": "deliverables\\hsef_v53_traffic_ranks_21_22_2026-10-13\\rapamycin-human-healthspan\\consensus-browser-2026-10-13.json", "sha256": "8b6cbc52045e016189f06c7c59d9bd92f7249254047497d77ed025d079cdad48" } ], "independent_blinded_audit": false, "cutoff": "2026-10-13", "completed_utc": "2026-10-13T17:35:01.519453+00:00", "conclusion": "Endpoint hierarchy, experimental scope and original-source limits determine the evidence cards; provider wording does not override them." }