Derivation Web

source_246ae8f2cd2a457c

by researka:v2 · 2026-06-22 01:14:48.555698+04:00

{"content_hash": "sha256:a97ba78bbc888543b0d060e786d0cbf8399269d95a404c9f5d7b656c53630c3b", "edges": [{"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_1", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_2", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_3", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_4", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_5", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_6", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_7", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_8", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_9", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_10", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_11", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_12", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_13", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_14", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_15", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_16", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_17", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_18", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_19", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_20", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_21", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_22", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_23", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_24", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_25", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_26", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_27", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_28", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_29", "type": "contains_claim"}, {"from": "55c23130-2789-4619-9045-518911e27dd1", "to": "claim_30", "type": "contains_claim"}], "nodes": [{"id": "55c23130-2789-4619-9045-518911e27dd1", "title": "Hypothesis-Generating Brief: Sirtuin Intervention Aging Effects — full paper", "type": "publication"}, {"id": "claim_1", "text": "Evidence-honesty note: 36/41 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. 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. 38/41 retained sources are indirect, review-level, adjacent, or mechanistic and 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 sirtuin intervention aging effects across 41 accepted source papers and 1394 high-confidence extracted claims.", "type": "claim"}, {"id": "claim_3", "text": "The evidence profile contains 3 direct clinical sources, 37 adjacent clinical sources, and 1 mechanistic or model-system source, with 116 cross-study disagreements across the evidence base.", "type": "claim"}, {"id": "claim_4", "text": "Positive study-level signals are summarized in the contextual adjacent evidence outcome class, null signals in the contextual adjacent evidence, cardiometabolic and deficiency prevalence outcome classes, and negative signals in the muscle function, immune and inflammation outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "type": "claim"}, {"id": "claim_5", "text": "The conclusion is that sirtuin intervention aging effects remains a bounded geroscience case: the retained clinical and mechanistic evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "type": "claim"}, {"id": "claim_6", "text": "For that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.", "type": "claim"}, {"id": "claim_7", "text": "This synthesis evaluates evidence on sirtuin intervention aging effects across 41 included source papers and 1394 high-confidence extracted claims. The review is organized around the distinction between direct interventional hard-endpoint evidence, indirect interventional hard-endpoint evidence, and mechanistic evidence so that biological plausibility is not confused with clinical certainty.", "type": "claim"}, {"id": "claim_8", "text": "The corpus contains 3 direct clinical sources, 37 adjacent clinical sources, and 1 mechanistic or model-system source. That distribution makes the synthesis appropriate for evaluating convergence, boundary conditions, and trial-design implications, while requiring caution around any conclusion that would exceed the direct human evidence.", "type": "claim"}, {"id": "claim_9", "text": "The thesis is: Across 41 curated reference papers, the evidence base for Sirtuin shows a context-dependent profile. Positive signals appear in: contextual other. Negative signals appear in: muscle function, immune. Null findings dominate: contextual other, cardiometabolic. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Sirtuin 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. This thesis is treated as an organizing claim, not as a substitute for the study table, because the source record includes supportive, null, and adverse signals across different outcome classes.", "type": "claim"}, {"id": "claim_10", "text": "This distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.", "type": "claim"}, {"id": "claim_11", "text": "The mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.", "type": "claim"}, {"id": "claim_12", "text": "Null findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.", "type": "claim"}, {"id": "claim_13", "text": "Adverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.", "type": "claim"}, {"id": "claim_14", "text": "The evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.", "type": "claim"}, {"id": "claim_15", "text": "The background evidence for sirtuin intervention aging effects is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Werida 2023, Daneshi-Maskooni 2017, Bo 2018 are interpreted separately from mechanistic studies such as Krekora 2026, because these evidence roles answer different questions about aging biology and clinical translation.", "type": "claim"}, {"id": "claim_16", "text": "The direct evidence establishes what has been observed in human or adjacent clinical settings. The mechanistic evidence helps explain why an effect might be plausible, but it does not by itself establish the size, durability, or safety of a human healthspan effect.", "type": "claim"}, {"id": "claim_17", "text": "Across the retained sources, positive signals cluster around the contextual adjacent evidence outcome class; null signals around the contextual adjacent evidence, cardiometabolic and deficiency prevalence outcome classes; and negative or adverse signals around the muscle function, immune and inflammation outcome classes. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "type": "claim"}, {"id": "claim_18", "text": "The study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.", "type": "claim"}, {"id": "claim_19", "text": "The resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.", "type": "claim"}, {"id": "claim_20", "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_21", "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_22", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, immune and inflammation, immune and inflammation, longevity, muscle function); 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_23", "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_24", "text": "Additional corpus sources included animal/preclinical evidence; Nowak-Szwed 2025: outcome=Cardiometabolic; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_25", "text": "Garcia-Martinez 2023: outcome=Contextual Adjacent Evidence; directness=indirect; tier=B2.", "type": "claim"}, {"id": "claim_26", "text": "Additional corpus sources included animal/preclinical evidence; substantive evidence synthesis: The manifest includes 41 retained sources, 3 direct-source row(s), and directional coding across negative=2, null=36, positive=1, unclear=2. Representative source-level signals are: Nowak-Szwed 2025: outcome=Cardiometabolic; direction=unclear; directness=indirect; tier=B2; claims=124; Wu 2022: outcome=Cardiometabolic; direction=unclear; directness=indirect; tier=B2; claims=106; Werida 2023: outcome=Contextual Adjacent Evidence; direction=positive; directness=direct; tier=A1; claims=80; Shi 2025: outcome=Muscle Function; direction=negative; directness=indirect; tier=B2; claims=11; Noureldein 2015: outcome=Immune and Inflammation; direction=negative; directness=review; tier=B1; claims=1; Garcia-Martinez 2023: outcome=Contextual Adjacent Evidence; direction=null; directness=indirect; tier=B2; claims=106; Zhang 2025: outcome=Contextual Adjacent Evidence; direction=null; directness=indirect; tier=B2; claims=82; Nguyen 2026: outcome=Deficiency Prevalence; direction=null; directness=indirect; tier=B2; claims=65. These signals inform the bounded conclusion by separating effect direction from evidence tier/directness; indirect, review-level, mechanistic, or contextual evidence remains hypothesis-generating.", "type": "claim"}, {"id": "claim_27", "text": "Additional corpus sources included animal/preclinical evidence; key findings from source synthesis: First, the strongest positive or favorable signals are treated as narrow source-level signals, not broad clinical proof (Nowak-Szwed 2025: outcome=Cardiometabolic; direction=unclear; directness=indirect; tier=B2; claims=124; Wu 2022: outcome=Cardiometabolic; direction=unclear; directness=indirect; tier=B2; claims=106; Werida 2023: outcome=Contextual Adjacent Evidence; direction=positive; directness=direct; tier=A1; claims=80). Second, negative, mixed, unclear, or no-directional-signal rows are given equal interpretive weight (Shi 2025: outcome=Muscle Function; direction=negative; directness=indirect; tier=B2; claims=11; Noureldein 2015: outcome=Immune and Inflammation; direction=negative; directness=review; tier=B1; claims=1; Garcia-Martinez 2023: outcome=Contextual Adjacent Evidence; direction=null; directness=indirect; tier=B2; claims=106). Third, the bounded conclusion follows from the balance of source direction, outcome class, evidence tier, and directness rather than from source count alone.", "type": "claim"}, {"id": "claim_28", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_29", "text": "| Contextual Adjacent Evidence | n=22; claims=779 | no extracted directional signal in 21/22 sources | 2 direct; 18 indirect; 1 protocol; 1 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_30", "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"}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12933-025-03013-y", "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": "Sirtuins and regulatory miRNAs as epigenetic determinants of empagliflozin-mediated recovery after acute myocardial infarction", "type": "source", "url": "https://doi.org/10.1186/s12933-025-03013-y", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms24087422", "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": "Effect of Resveratrol on Markers of Oxidative Stress and Sirtuin 1 in Elderly Adults with Type 2 Diabetes", "type": "source", "url": "https://doi.org/10.3390/ijms24087422", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41392-022-01257-8", "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": "The sirtuin family in health and disease", "type": "source", "url": "https://doi.org/10.1038/s41392-022-01257-8", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1021/acsomega.5c03880", "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": "Epigallocatechin-3-Gallate from Green Tea Reduces Vascular Aging and Endothelial Cell Senescence by Modifying Autophagy and Ferroptosis through the Sirtuin 1 Signaling Pathway", "type": "source", "url": "https://doi.org/10.1021/acsomega.5c03880", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12902-023-01511-2", "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": "Effect of coadministration of omega-3 fatty acids with glimepiride on glycemic control, lipid profile, irisin, and sirtuin-1 in type 2 diabetes mellitus patients: a randomized controlled trial", "type": "source", "url": "https://doi.org/10.1186/s12902-023-01511-2", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/acel.70457", "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": "Endothelial Sirtuins and Mitochondrial Function Are Associated With Testosterone Status: Implications for Accelerated Vascular Aging in Middle‐Age and Older Men With Low Testosterone", "type": "source", "url": "https://doi.org/10.1111/acel.70457", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41387-021-00168-x", "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": "The effect of daily intake of vitamin D-fortified yogurt drink, with and without added calcium, on serum adiponectin and sirtuins 1 and 6 in adult subjects with type 2 diabetes", "type": "source", "url": "https://doi.org/10.1038/s41387-021-00168-x", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.7759/cureus.82663", "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": "Sirtuin Expression in Age-Associated Hepatic Response to Burn Trauma: Translational and Clinical Insights From a Murine Model", "type": "source", "url": "https://doi.org/10.7759/cureus.82663", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/nu13113824", "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": "Impact of Dietary Modifications on Plasma Sirtuins 1, 3 and 5 in Older Overweight Individuals Undergoing 12-Weeks of Circuit Training", "type": "source", "url": "https://doi.org/10.3390/nu13113824", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12937-019-0518-3", "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": "Effects of cinnamon supplementation on expression of systemic inflammation factors, NF-kB and Sirtuin-1 (SIRT1) in type 2 diabetes: a randomized, double blind, and controlled clinical trial", "type": "source", "url": "https://doi.org/10.1186/s12937-019-0518-3", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/biom10101414", "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": "Changes in the Systemic Expression of Sirtuin-1 and Oxidative Stress after Intravitreal Anti-Vascular Endothelial Growth Factor in Patients with Retinal Vein Occlusion", "type": "source", "url": "https://doi.org/10.3390/biom10101414", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12903-025-06690-z", "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": "Taurine, Sirtuin-1 and TNF- α levels in different aged adults with periodontitis: a pilot study", "type": "source", "url": "https://doi.org/10.1186/s12903-025-06690-z", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/molecules31071182", "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": "Sechium edule var. nigrum spinosum (Chayote) Increases the mRNA Expression of Genes Encoding Sirtuins in Older Adults with Type 2 Diabetes Mellitus", "type": "source", "url": "https://doi.org/10.3390/molecules31071182", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijerph191811292", "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": "Impact of Exercise Intensity on Systemic Oxidative Stress, Inflammatory Responses, and Sirtuin Levels in Healthy Male Volunteers", "type": "source", "url": "https://doi.org/10.3390/ijerph191811292", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/cimb48030314", "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": "Effects of Citicoline-Based Supplementation on Lipid Peroxidation Markers and Sirtuin-1 Expression in Ischemic Stroke", "type": "source", "url": "https://doi.org/10.3390/cimb48030314", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.21470/1678-9741-2024-0218", "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": "The Relationship Between Aortic Tissue Sirtuin 1 Levels and Type A Aortic Dissections and Ascending Aortic Aneurysms", "type": "source", "url": "https://doi.org/10.21470/1678-9741-2024-0218", "year": 2025}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1155/jdr/5528647", "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": "Deciphering the Role of Sirtuin‐1 Gene Polymorphism in Diabetic Nephropathy: A Systematic Review and Meta‐Analysis", "type": "source", "url": "https://doi.org/10.1155/jdr/5528647", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/jcm15041485", "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": "Association Between Salivary Sirtuin-1 Levels and Periodontitis", "type": "source", "url": "https://doi.org/10.3390/jcm15041485", "year": 2026}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1002/cpdd.1488", "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": "Phase 1, Single‐Center, Double‐Blind, Randomized, Placebo‐Controlled Studies of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of the Sirtuin 6 Activator SP‐624 in Healthy Adults", "type": "source", "url": "https://doi.org/10.1002/cpdd.1488", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s00414-025-03626-8", "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": "Evaluation of Sirtuin 1 (SIRT1) and Sirtuin 3 (SIRT3) in serum and cerebrospinal fluid following fatal traumatic brain injury", "type": "source", "url": "https://doi.org/10.1007/s00414-025-03626-8", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms22052331", "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": "Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans", "type": "source", "url": "https://doi.org/10.3390/ijms22052331", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms26189033", "effect": "not extracted", "endpoint": "not extracted", "id": "source_22", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Elevated Sirtuin 1 Levels in Patients with Chronic Kidney Disease, Including on Peritoneal Dialysis: Associations with Cardiovascular Risk and Peritoneal Fibrosis", "type": "source", "url": "https://doi.org/10.3390/ijms26189033", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41366-025-02007-w", "effect": "not extracted", "endpoint": "not extracted", "id": "source_23", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The effect of obesity and aging on NAD + /Sirtuin metabolism transcription and DNA methylation in subcutaneous adipose tissue of monozygotic twin pairs discordant for BMI", "type": "source", "url": "https://doi.org/10.1038/s41366-025-02007-w", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/cells14211675", "effect": "not extracted", "endpoint": "not extracted", "id": "source_24", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Irisin Increases Sirtuin 1 to Improve Glucocorticoid-Induced Sarcopenia and Mitochondrial Dysfunction", "type": "source", "url": "https://doi.org/10.3390/cells14211675", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s12276-021-00687-8", "effect": "not extracted", "endpoint": "not extracted", "id": "source_25", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Upregulating sirtuin 6 ameliorates glycolysis, EMT and distant metastasis of pancreatic adenocarcinoma with krüppel-like factor 10 deficiency", "type": "source", "url": "https://doi.org/10.1038/s12276-021-00687-8", "year": 2021}, {"comparator": "not extracted", "directness": "primary", "doi": "10.7150/thno.49770", "effect": "not extracted", "endpoint": "not extracted", "id": "source_26", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Statin suppresses sirtuin 6 through miR-495, increasing FoxO1-dependent hepatic gluconeogenesis", "type": "source", "url": "https://doi.org/10.7150/thno.49770", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s13006-020-00301-z", "effect": "not extracted", "endpoint": "not extracted", "id": "source_27", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Effects of perinatal factors on sirtuin 3, 8-hydroxy-2′- deoxyguanosine, brain-derived neurotrophic factor and serotonin in cord blood and early breast milk: an observational study", "type": "source", "url": "https://doi.org/10.1186/s13006-020-00301-z", "year": 2020}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/molecules30183740", "effect": "not extracted", "endpoint": "not extracted", "id": "source_28", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Can Sirtuin 1 Serve as a Therapeutic Target in Pulmonary Arterial Hypertension? A Comprehensive Review", "type": "source", "url": "https://doi.org/10.3390/molecules30183740", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fmmed.2026.1818104", "effect": "not extracted", "endpoint": "not extracted", "id": "source_29", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Sirtuin 1 is a key molecular link between cellular senescence and heart failure", "type": "source", "url": "https://doi.org/10.3389/fmmed.2026.1818104", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41598-024-78576-z", "effect": "not extracted", "endpoint": "not extracted", "id": "source_30", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Evaluation of sirtuin 1 as a predictor of cardiovascular outcomes in diabetic patients with limb-threatening ischemia", "type": "source", "url": "https://doi.org/10.1038/s41598-024-78576-z", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.2174/0118746098319674240827104612", "effect": "not extracted", "endpoint": "not extracted", "id": "source_31", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Nicotinamide Adenine Dinucleotide (NAD)-Dependent Protein Deacetylase, Sirtuin, as a Biomarker of Healthy Life Expectancy: A Mini-Review", "type": "source", "url": "https://doi.org/10.2174/0118746098319674240827104612", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1155/2014/871263", "effect": "not extracted", "endpoint": "not extracted", "id": "source_32", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The Sirtuin 3 Expression Profile Is Associated with Pathological and Clinical Outcomes in Colon Cancer Patients", "type": "source", "url": "https://doi.org/10.1155/2014/871263", "year": 2014}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1371/journal.pone.0159801", "effect": "not extracted", "endpoint": "not extracted", "id": "source_33", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The Prognostic and Clinicopathological Roles of Sirtuin-3 in Various Cancers", "type": "source", "url": "https://doi.org/10.1371/journal.pone.0159801", "year": 2016}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/nu10070937", "effect": "not extracted", "endpoint": "not extracted", "id": "source_34", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Gene Expression of Sirtuin-1 and Endogenous Secretory Receptor for Advanced Glycation End Products in Healthy and Slightly Overweight Subjects after Caloric Restriction and Resveratrol Administration", "type": "source", "url": "https://doi.org/10.3390/nu10070937", "year": 2018}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s13063-017-1979-3", "effect": "not extracted", "endpoint": "not extracted", "id": "source_35", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The effects of green cardamom on blood glucose indices, lipids, inflammatory factors, paraxonase-1, sirtuin-1, and irisin in patients with nonalcoholic fatty liver disease and obesity: study protocol for a randomized controlled trial", "type": "source", "url": "https://doi.org/10.1186/s13063-017-1979-3", "year": 2017}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms21010295", "effect": "not extracted", "endpoint": "not extracted", "id": "source_36", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women", "type": "source", "url": "https://doi.org/10.3390/ijms21010295", "year": 2019}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1177/0300060518811228", "effect": "not extracted", "endpoint": "not extracted", "id": "source_37", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Serum and follicular fluid levels of sirtuin 1, sirtuin 6, and resveratrol in women undergoing in vitro fertilization: an observational, clinical study", "type": "source", "url": "https://doi.org/10.1177/0300060518811228", "year": 2019}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12906-017-2068-6", "effect": "not extracted", "endpoint": "not extracted", "id": "source_38", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "The effects of green cardamom supplementation on blood glucose, lipids profile, oxidative stress, sirtuin-1 and irisin in type 2 diabetic patients: a study protocol for a randomized placebo-controlled clinical trial", "type": "source", "url": "https://doi.org/10.1186/s12906-017-2068-6", "year": 2018}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s00592-017-1097-4", "effect": "not extracted", "endpoint": "not extracted", "id": "source_39", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Impact of sirtuin-1 expression on H3K56 acetylation and oxidative stress: a double-blind randomized controlled trial with resveratrol supplementation", "type": "source", "url": "https://doi.org/10.1007/s00592-017-1097-4", "year": 2018}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1097/MD.0000000000002238", "effect": "not extracted", "endpoint": "not extracted", "id": "source_40", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Single Nucleotide Polymorphisms of the Sirtuin 1 (SIRT1) Gene are Associated With age-Related Macular Degeneration in Chinese Han Individuals", "type": "source", "url": "https://doi.org/10.1097/MD.0000000000002238", "year": 2015}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.1016/j.diabres.2015.05.043", "effect": "not extracted", "endpoint": "not extracted", "id": "source_41", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "Fenofibrate reduces inflammation in obese patients with or without type 2 diabetes mellitus via sirtuin 1/fetuin A axis.", "type": "source", "url": "https://doi.org/10.1016/j.diabres.2015.05.043", "year": 2015}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_42", "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_43", "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_44", "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_45", "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": "10.1371/journal.pmed.0020124", "effect": "not extracted", "endpoint": "not extracted", "id": "source_46", "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": "55c23130-2789-4619-9045-518911e27dd1", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 41, "included": 41, "included_or_retained": 41, "screened": 41, "wording": "41 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": "55c23130-2789-4619-9045-518911e27dd1",
  "researka_submission_id": "75c23474-39a9-49c5-98a3-25e8a95b8f65",
  "sidecar_name": "claim_graph.json",
  "sidecar_url": "https://api.researka.org/publications/55c23130-2789-4619-9045-518911e27dd1/sidecars/claim_graph.json"
}