Derivation Web

source_50bd30de22a94ca5

by researka:v2 · 2026-06-05 22:14:08.974289+04:00

{"content_hash": null, "edges": [{"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_1", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_2", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_3", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_4", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_5", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_6", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_7", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_8", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_9", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_10", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_11", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_12", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_13", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_14", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_15", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_16", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_17", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_18", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_19", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_20", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_21", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_22", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_23", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_24", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_25", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_26", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_27", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_28", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_29", "type": "contains_claim"}, {"from": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "to": "claim_30", "type": "contains_claim"}], "nodes": [{"id": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "title": "Research Synthesis: Longevity Lifespan Effects — full paper", "type": "publication"}, {"id": "claim_1", "text": "The evidence profile contains no sources classified primarily as direct clinical evidence, 6 adjacent clinical sources, and 2 mechanistic or model-system sources, with 34 cross-study disagreements across the evidence base.", "type": "claim"}, {"id": "claim_2", "text": "Positive study-level signals are summarized in the longevity outcome class, null signals in the contextual adjacent evidence and longevity outcome classes, and negative signals in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "type": "claim"}, {"id": "claim_3", "text": "The conclusion is that longevity lifespan effects should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "type": "claim"}, {"id": "claim_4", "text": "This manuscript is reported as a Thin-corpus evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-longevity_lifespan_effects-v06-DAILY-2026-06-05T18-08-31Z`.", "type": "claim"}, {"id": "claim_5", "text": "The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.", "type": "claim"}, {"id": "claim_6", "text": "Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.", "type": "claim"}, {"id": "claim_7", "text": "Evidence-tension synthesis: claims grouped by outcome class (contextual adjacent evidence, longevity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.", "type": "claim"}, {"id": "claim_8", "text": "Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.", "type": "claim"}, {"id": "claim_9", "text": "The retained longevity lifespan effects corpus is reported by outcome class before any cross-domain interpretation. This structure prevents favorable, null, mixed, and adverse evidence from being blended across biologically different endpoints.", "type": "claim"}, {"id": "claim_10", "text": "The longevity evidence packet includes 8 source-level summaries and 240 high-confidence observations. Directional coding within this packet is null=3, positive=1, unclear=4, and directness coding is indirect=5, mechanistic=2, review=1. These counts describe the frozen evidence state for this outcome, not a pooled treatment estimate.", "type": "claim"}, {"id": "claim_11", "text": "The contextual adjacent evidence evidence packet includes 5 source-level summaries and 78 high-confidence observations. Directional coding within this packet is null=5, and directness coding is indirect=1, review=4. These counts describe the frozen evidence state for this outcome, not a pooled treatment estimate.", "type": "claim"}, {"id": "claim_12", "text": "Across outcome classes, the manuscript treats disagreement as part of the evidence rather than as noise to smooth away. A null or adverse signal in one section does not cancel a favorable signal in another; it defines the boundary condition for interpretation.", "type": "claim"}, {"id": "claim_13", "text": "Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.", "type": "claim"}, {"id": "claim_14", "text": "The curated corpus contains no long-term mortality randomized controlled trial in human adults. The included longevity studies rely on preclinical invertebrate models (Heath 2026; Zheng 2026; ColerReilly 2025) or large-scale observational cohorts in athletes (Altulea 2024), leaving a critical evidentiary gap between mechanistic lifespan extension and confirmed all-cause mortality benefit in general populations. IvimeyCook 2025, a vertebrate meta-analysis of rapamycin and metformin, also relies on animal data rather than human trials. Without a dedicated human mortality endpoint trial, the headline conclusion that any intervention causally extends human lifespan cannot be made; current estimates are subject to the well-documented risk that surrogate associations do not guarantee hard-outcome validity (Ioannidis 2005).", "type": "claim"}, {"id": "claim_15", "text": "Several outcome claims rest on a single source, precluding internal replication within this corpus. Single-trial evidence, even when mechanistically plausible, carries substantial risk of confounding and limits the generalizability of any claim made in this synthesis.", "type": "claim"}, {"id": "claim_16", "text": "Additional corpus sources included animal/preclinical evidence; the endpoint landscape is narrow: no study in this corpus measured cause-specific mortality, health-adjusted life expectancy, or quality-of-life trajectories across the lifespan. Several included papers (Wong 2026; Ho 2026; Khalil 2025; Sensi 2026) address contextual or device-related lifespan rather than biological aging, and thus contribute no evidence to the anti-aging thesis. Mechanistic autophagy markers reported by Heath 2026 in C. elegans (increased autophagic flux) are biologically informative but remain far from clinically validated surrogates for human longevity.", "type": "claim"}, {"id": "claim_17", "text": "For longevity lifespan effects, the final interpretation is deliberately tiered: the retained clinical and adjacent evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation.The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.", "type": "claim"}, {"id": "claim_18", "text": "This synthesis maps 13 included sources on Longevity Lifespan Effects across 2 outcome classes and 34 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.", "type": "claim"}, {"id": "claim_19", "text": "Across 13 curated reference papers, the evidence base for Longevity Lifespan Effects shows a context-dependent profile. Positive signals appear in: longevity. Null findings dominate: contextual adjacent evidence, longevity. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Longevity Lifespan Effects anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.", "type": "claim"}, {"id": "claim_20", "text": "The strongest unresolved contrast is the null vs positive between Boominathan 2025 and IvimeyCook 2025 on longevity (severity 3/5), which defines the boundary condition future studies must test rather than smooth over.", "type": "claim"}, {"id": "claim_21", "text": "This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.", "type": "claim"}, {"id": "claim_22", "text": "| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |", "type": "claim"}, {"id": "claim_23", "text": "| longevity | 0 | 8 | null, positive, unclear | direct interventional hard-endpoint gap |", "type": "claim"}, {"id": "claim_24", "text": "| contextual adjacent evidence | 0 | 5 | null | direct interventional hard-endpoint gap |", "type": "claim"}, {"id": "claim_25", "text": "| P1 | longevity: direct interventional hard-endpoint gap | 0 direct and 8 indirect sources; direction profile: null, positive, unclear |", "type": "claim"}, {"id": "claim_26", "text": "| P2 | contextual adjacent evidence: direct interventional hard-endpoint gap | 0 direct and 5 indirect sources; direction profile: null |", "type": "claim"}, {"id": "claim_27", "text": "The next high-yield study for Longevity Lifespan Effects should target the **longevity** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 200 participants per arm, a priority population of adults or older adults with baseline risk in the target outcome domain, and follow-up lasting at least 12 months; shorter or smaller studies should be treated as hypothesis-generating.", "type": "claim"}, {"id": "claim_28", "text": "The manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.", "type": "claim"}, {"id": "claim_29", "text": "IvimeyCook 2025; tier=B2; directness=indirect; endpoint=longevity; direction=null; representative statistic=P < 0.001.", "type": "claim"}, {"id": "claim_30", "text": "Sensi 2026; tier=B2; directness=indirect; endpoint=contextual adjacent evidence; direction=null.", "type": "claim"}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1111/acel.14392", "effect": "not extracted", "endpoint": "not extracted", "id": "source_1", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The impact of cysteine on lifespan in three model organisms: A systematic review and meta‐analysis", "type": "source", "url": "https://doi.org/10.1111/acel.14392", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/microorganisms14020314", "effect": "not extracted", "endpoint": "not extracted", "id": "source_2", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Multi-Model Longevity Assays Reveal Lifespan- and Healthspan-Promoting Effects of Bacillus subtilis WTC019", "type": "source", "url": "https://doi.org/10.3390/microorganisms14020314", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/acel.70225", "effect": "not extracted", "endpoint": "not extracted", "id": "source_3", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Six Drivers of Aging Identified Among Genes Differentially Expressed With Age", "type": "source", "url": "https://doi.org/10.1111/acel.70225", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/acel.70131", "effect": "not extracted", "endpoint": "not extracted", "id": "source_4", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Rapamycin, Not Metformin, Mirrors Dietary Restriction‐Driven Lifespan Extension in Vertebrates: A Meta‐Analysis", "type": "source", "url": "https://doi.org/10.1111/acel.70131", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fpubh.2026.1735033", "effect": "not extracted", "endpoint": "not extracted", "id": "source_5", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Budget impact analysis of deep brain stimulation devices with different longevity in Parkinson's disease: insights from real-world data", "type": "source", "url": "https://doi.org/10.3389/fpubh.2026.1735033", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fpsyg.2026.1722743", "effect": "not extracted", "endpoint": "not extracted", "id": "source_6", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "A systematic review and meta-analysis of the effects of errorless motor learning on movement outcomes: a lifespan and impairment perspective", "type": "source", "url": "https://doi.org/10.3389/fpsyg.2026.1722743", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s11357-024-01307-9", "effect": "not extracted", "endpoint": "not extracted", "id": "source_7", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Sport and longevity: an observational study of international athletes", "type": "source", "url": "https://doi.org/10.1007/s11357-024-01307-9", "year": 2024}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1002/cnr2.70507", "effect": "not extracted", "endpoint": "not extracted", "id": "source_8", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The Effect of Interferon Type I Adjuvant Therapy on the Lifespan and Complications of Glioma Patients Undergoing Chemotherapy: A Systematic Review and Meta‐Analysis", "type": "source", "url": "https://doi.org/10.1002/cnr2.70507", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3390/ijerph22050690", "effect": "not extracted", "endpoint": "not extracted", "id": "source_9", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Green Environments for Sustainable Brains: Parameters Shaping Adaptive Neuroplasticity and Lifespan Neurosustainability—A Systematic Review and Future Directions", "type": "source", "url": "https://doi.org/10.3390/ijerph22050690", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1136/bmjopen-2025-115862", "effect": "not extracted", "endpoint": "not extracted", "id": "source_10", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Prefilled versus infused regional citrate anticoagulation during continuous renal replacement therapy on circuit lifespan: protocol for a randomised controlled trial", "type": "source", "url": "https://doi.org/10.1136/bmjopen-2025-115862", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fpsyg.2026.1745013", "effect": "not extracted", "endpoint": "not extracted", "id": "source_11", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The influence of attachment and relational quality on developmental outcomes across the lifespan: a systematic review and meta-analytic insights (2014–2024)", "type": "source", "url": "https://doi.org/10.3389/fpsyg.2026.1745013", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/biom16010073", "effect": "not extracted", "endpoint": "not extracted", "id": "source_12", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Novel tRNA Synthetase Inhibitors Increase Healthspan, Lifespan, and Autophagic Flux in C. elegans", "type": "source", "url": "https://doi.org/10.3390/biom16010073", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1101/2025.11.03.686437", "effect": "not extracted", "endpoint": "not extracted", "id": "source_13", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Estrogen-Mediated Suppression of IL-11 as a Hormonal Mechanism Underlying Female Longevity Advantage", "type": "source", "url": "https://doi.org/10.1101/2025.11.03.686437", "year": 2025}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_14", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_15", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_16", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_17", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "**Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.", "type": "source", "url": null, "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1136/bmj.c332", "effect": "not extracted", "endpoint": "not extracted", "id": "source_18", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Schulz 2010", "type": "source", "url": "https://doi.org/10.1136/bmj.c332", "year": null}, {"comparator": "not extracted", "directness": "citation", "doi": "10.1371/journal.pmed.0020124", "effect": "not extracted", "endpoint": "not extracted", "id": "source_19", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Ioannidis 2005", "type": "source", "url": "https://doi.org/10.1371/journal.pmed.0020124", "year": null}], "publication_id": "9dac2b04-d8de-4675-a8de-11480ceb67ae", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 13, "included": 13, "included_or_retained": 13, "screened": 13, "wording": "13 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit."}}

{
  "researka_object_type": "publication_sidecar",
  "researka_publication_id": "9dac2b04-d8de-4675-a8de-11480ceb67ae",
  "researka_submission_id": "6dbb019b-4832-4d74-abbe-115b8f5ce1b2",
  "sidecar_name": "claim_graph.json",
  "sidecar_url": "https://api.researka.org/publications/9dac2b04-d8de-4675-a8de-11480ceb67ae/sidecars/claim_graph.json"
}