Derivation Web

source_6ebd364260b54e0f

by researka:v2 · 2026-06-28 02:18:53.975833+04:00

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Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.", "type": "claim"}, {"id": "claim_2", "text": "This paper synthesizes evidence on SASP secretome across 17 accepted source papers and 193 high-confidence extracted claims.", "type": "claim"}, {"id": "claim_3", "text": "The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 16 adjacent clinical sources, and 1 mechanistic or model-system source, with 3 cross-study disagreements across the evidence base.", "type": "claim"}, {"id": "claim_4", "text": "Positive study-level signals are summarized in the longevity outcome class, null signals in the contextual adjacent evidence, immune and inflammation, longevity outcome classes, and negative signals in the immune and inflammation outcome class. The paper therefore reports a source-directness and outcome-class map rather than a pooled effect.", "type": "claim"}, {"id": "claim_5", "text": "The conclusion is narrower: the retained evidence maps associations, mechanisms, and candidate endpoints for follow-up; it does not establish clinical benefit, therapeutic actionability, or anti-aging efficacy.", "type": "claim"}, {"id": "claim_6", "text": "This manuscript is reported as a 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-sasp_secretome-v06-DAILY-2026-06-26T20-06-36Z`.", "type": "claim"}, {"id": "claim_7", "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 sidecar when populated, and claim registry) rather than from re-parsed full text.", "type": "claim"}, {"id": "claim_8", "text": "Risk-of-bias framework assignment follows study design (RoB-2 for RCTs, ROBINS-I for non-randomised studies, AMSTAR-2 for systematic reviews / meta-analyses). Public appraisal claims are limited to populated `risk_of_bias.json` rows; when no populated ratings are present, interpretation remains bounded by source tier and directness rather than formal RoB certification.", "type": "claim"}, {"id": "claim_9", "text": "Evidence-tension synthesis: claims grouped by outcome class (contextual adjacent evidence, immune and inflammation, 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_10", "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_11", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_12", "text": "| SASP secretome / Contextual Adjacent Evidence | n=10; claims=92 | significant source statistic in 5/10 sources; receipt-level direction coded null | 9 indirect; 1 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_13", "text": "| SASP secretome / Immune and Inflammation | n=5; claims=86 | significant source statistic in 3/5 sources; receipt-level direction coded null | 3 indirect; 1 mechanistic; 1 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_14", "text": "Aging and geroscience context: 4 sources; significant source statistic in 1/4 sources; receipt-level direction coded null.", "type": "claim"}, {"id": "claim_15", "text": "Oncology and cancer context: 4 sources; significant source statistic in 3/4 sources; receipt-level direction coded null.", "type": "claim"}, {"id": "claim_16", "text": "Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.", "type": "claim"}, {"id": "claim_17", "text": "Additional corpus sources included animal/preclinical evidence; contextual Adjacent Evidence remains a separate Results slice for SASP secretome (n=10; claims=92; significant source statistic in 5/10 sources; receipt-level direction coded null; 9 indirect; 1 review; limited corpus depth in this outcome class) and is not pooled into adjacent endpoint classes. Source-level findings are:", "type": "claim"}, {"id": "claim_18", "text": "Zhang 2019 (Folic Acid Supplementation Suppresses Sleep Deprivation-Induced Telomere Dysfunction and Senescence-Associated; representative statistic P < 0.05; source-level statistic reported; direction=null; directness=indirect; tier=B2).", "type": "claim"}, {"id": "claim_19", "text": "Coppe 2008 (Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor; representative statistic p > 0.05; source-level statistic reported; direction=null; directness=indirect; tier=B2).", "type": "claim"}, {"id": "claim_20", "text": "Niklander 2020 (ROCK inhibition modulates the senescence‐associated secretory phenotype (SASP) in oral keratinocytes; representative statistic P > 0.05; source-level statistic reported; direction=null; directness=indirect; tier=B2).", "type": "claim"}, {"id": "claim_21", "text": "Direction reconciliation: receipt-level null or unclear coding is conservative claim-level coding. Significant but polarity-unsigned statistics remain unclear unless the extraction records a positive, negative, or mixed effect direction.", "type": "claim"}, {"id": "claim_22", "text": "Immune and Inflammation remains a separate Results slice for SASP secretome (n=5; claims=86; significant source statistic in 3/5 sources; receipt-level direction coded null; 3 indirect; 1 mechanistic; 1 review; limited corpus depth in this outcome class) and is not pooled into adjacent endpoint classes. Source-level findings are:", "type": "claim"}, {"id": "claim_23", "text": "Sanchez-Romero 2026 (Evidence gaps in the effects of exercise on SASP-Related biomarkers in older adults: a systematic review and; 30 extracted claim(s); receipt-level direction is the coded finding; direction=null; directness=review; tier=B2).", "type": "claim"}, {"id": "claim_24", "text": "Additional corpus sources included animal/preclinical evidence; longevity remains a separate Results slice for SASP secretome (n=2; claims=15; positive signal in 1/2 sources; 2 indirect; limited corpus depth in this outcome class) and is not pooled into adjacent endpoint classes. Source-level findings are:", "type": "claim"}, {"id": "claim_25", "text": "Alam 2025 (The Impact of Senescence-Associated Secretory Phenotype (SASP) on Head and Neck Cancers: From Biology to Therapy; 1 extracted claim(s); receipt-level direction is the coded finding; direction=null; directness=indirect; tier=B2).", "type": "claim"}, {"id": "claim_26", "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_27", "text": "The principal limitation is evidence-role imbalance. The retained corpus contains no sources classified primarily as direct interventional hard-endpoint evidence, 16 adjacent clinical sources, and 1 mechanistic or model-system source, which means causal interpretation depends on how much weight is assigned to each evidence tier.", "type": "claim"}, {"id": "claim_28", "text": "A second limitation is endpoint heterogeneity. Study-level signals span the longevity outcome class, the contextual adjacent evidence, immune and inflammation, longevity outcome classes, the immune and inflammation outcome class, and no dominant outcome class; these domains cannot be pooled narratively without losing clinically relevant differences in measurement, population, and study design.", "type": "claim"}, {"id": "claim_29", "text": "The conclusion is narrower: the retained evidence maps associations, mechanisms, and candidate endpoints for follow-up; it does not establish clinical benefit, therapeutic actionability, or anti-aging efficacy. 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_30", "text": "This synthesis maps 17 included sources on Sasp Secretome across 4 outcome classes and 3 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"}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1186/s12877-026-07025-5", "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": "Evidence gaps in the effects of exercise on SASP-Related biomarkers in older adults: a systematic review and meta-analysis of randomized controlled trials", "type": "source", "url": "https://doi.org/10.1186/s12877-026-07025-5", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms21124454", "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": "The microRNA-34a-Induced Senescence-Associated Secretory Phenotype (SASP) Favors Vascular Smooth Muscle Cells Calcification", "type": "source", "url": "https://doi.org/10.3390/ijms21124454", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1158/1538-7445.am2024-2954", "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": "Abstract 2954: Androgen deprivation therapy (ADT) and senescence-associated secretory phenotype (SASP) in vitro: Correlation with SASP in tumor specimens as well as in the serum of patients after ADT", "type": "source", "url": "https://doi.org/10.1158/1538-7445.am2024-2954", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12967-026-08221-y", "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": "Synergistic senolytic–regenerative therapy significantly extends healthspan and lifespan", "type": "source", "url": "https://doi.org/10.1186/s12967-026-08221-y", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/dme.70059", "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": "The cardio‐renal‐metabolic role of the nod‐like receptor protein‐3 and senescence‐associated secretory phenotype in early sodium/glucose cotransporter‐2 inhibitor therapy in people with diabetes who have had a myocardial infarction", "type": "source", "url": "https://doi.org/10.1111/dme.70059", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fimmu.2022.1019313", "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": "Senescence-associated secretory phenotype and its impact on oral immune homeostasis", "type": "source", "url": "https://doi.org/10.3389/fimmu.2022.1019313", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s12094-023-03364-6", "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": "Senescence in head and neck squamous cell carcinoma: relationship between senescence-associated secretory phenotype (SASP) mRNA expression level and clinicopathological features", "type": "source", "url": "https://doi.org/10.1007/s12094-023-03364-6", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/2211-5463.13012", "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": "ROCK inhibition modulates the senescence‐associated secretory phenotype (SASP) in oral keratinocytes", "type": "source", "url": "https://doi.org/10.1002/2211-5463.13012", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1093/gerona/glad265", "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": "Proteomic Analysis of the Senescence-Associated Secretory Phenotype: GDF-15, IGFBP-2, and Cystatin-C Are Associated With Multiple Aging Traits", "type": "source", "url": "https://doi.org/10.1093/gerona/glad265", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1093/geroni/igaf122.3519", "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": "A Senescence Associated Secretory Phenotype (SASP) in Indolent Systemic Mastocytosis Compared to Healthy Controls", "type": "source", "url": "https://doi.org/10.1093/geroni/igaf122.3519", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/alz.092727", "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": "Senescence‐associated secretory phenotype (SASP) index in individuals across the Alzheimer’s disease continuum", "type": "source", "url": "https://doi.org/10.1002/alz.092727", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.2147/PTT.S598115", "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": "Inflammaging and Senescence-Associated Secretory Phenotype (SASP) in Psoriasis – A Narrative Review of Potential Mechanisms and Anti-Inflammaging Strategies", "type": "source", "url": "https://doi.org/10.2147/PTT.S598115", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/cancers17244024", "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": "The Impact of Senescence-Associated Secretory Phenotype (SASP) on Head and Neck Cancers: From Biology to Therapy", "type": "source", "url": "https://doi.org/10.3390/cancers17244024", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/antiox12111956", "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": "Senescent Endothelial Cells Sustain Their Senescence-Associated Secretory Phenotype (SASP) through Enhanced Fatty Acid Oxidation", "type": "source", "url": "https://doi.org/10.3390/antiox12111956", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1155/2019/4569614", "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": "Folic Acid Supplementation Suppresses Sleep Deprivation-Induced Telomere Dysfunction and Senescence-Associated Secretory Phenotype (SASP)", "type": "source", "url": "https://doi.org/10.1155/2019/4569614", "year": 2019}, {"comparator": "not extracted", "directness": "primary", "doi": "10.18632/aging.101452", "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": "Small extracellular vesicles and their miRNA cargo are anti-apoptotic members of the senescence-associated secretory phenotype", "type": "source", "url": "https://doi.org/10.18632/aging.101452", "year": 2018}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1371/journal.pbio.0060301", "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": "Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor", "type": "source", "url": "https://doi.org/10.1371/journal.pbio.0060301", "year": 2008}, {"comparator": "not extracted", "directness": "citation", "doi": null, "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": "**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_19", "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_20", "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_21", "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}], "publication_id": "9b717300-cdd0-4406-84b9-c92f5e1c17ec", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 17, "included": 17, "included_or_retained": 17, "screened": 17, "wording": "17 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit."}}

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