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by researka:v2 · 2026-06-24 21:32:59.556605+04:00
{"publication_id": "073c460c-0262-46c7-88e4-bc96b9c25668", "traces": [{"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "We conducted an AI-assisted structured evidence synthesis of 60 curated reference papers, applying a source-level audit trail that links every numeric claim to its source and flags cross-domain tensions across outcome classes (immune, longevity, cardiometabolic, contextual other).", "claim_id": "claim_1"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Across the corpus, the evidence supports inflammaging as a biologically grounded, biomarker-detectable phenomenon whose clinical translation remains incomplete: mechanistic plausibility coexists with mixed or sparse human RCT evidence, longevity-relevant cohorts (Ceolin 2025 vs Spray 2025) disagree in direction, and boundary conditions across populations, exposures, and supplement classes are not yet established.", "claim_id": "claim_2"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "This paper synthesizes evidence on Chronic low-grade inflammation across 60 accepted source papers and 1409 high-confidence extracted claims.", "claim_id": "claim_3"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "The evidence profile contains 2 direct clinical sources, 54 adjacent clinical sources, and 4 mechanistic or model-system sources, with 163 cross-study disagreements across the evidence base.", "claim_id": "claim_4"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Positive study-level signals are summarized in the immune and inflammation, contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, immune and inflammation, longevity outcome classes, and negative signals in the immune and inflammation, longevity outcome classes. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "claim_id": "claim_5"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "The conclusion is that Chronic low-grade inflammation 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.", "claim_id": "claim_6"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "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.", "claim_id": "claim_7"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "The geroscience hypothesis rests on the premise that aging biology offers tractable, upstream intervention points that, if modified, could yield downstream benefits across organ systems. Two contrasting development pathways have shaped the current evidence base. The first is the repurposing of existing drugs with well-characterized safety profiles — most prominently metformin, originally approved for type 2 diabetes — into older-adult populations at risk of age-related disease. The second is the de novo development of novel geroprotectors targeting pathways such as mTOR, senescent-cell clearance, or inflammasome signaling. Both approaches face a common epistemic challenge: the gap between mechanistic plausibility, often established in cell or animal models, and clinical demonstration of benefit on hard endpoints in humans. Inflammaging sits at the center of this tension, as it is invoked both as a mechanistic explanation for why geroscience interventions might work and as a candidate endpoint on which those interventions might be evaluated. Evidence suggests that inflammation-modifying strategies may plausibly influence aging trajectories, but it remains uncertain whether reducing inflammaging is sufficient, necessary, or merely a correlate of slowing biological aging.", "claim_id": "claim_8"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "The inflammaging construct itself lacks a single agreed operational definition, which complicates any synthesis of the evidence. Across the available literature, inflammaging is variably described in terms of elevated circulating cytokines such as IL-6, acute-phase reactants including C-reactive protein, immune-cell phenotypic shifts, or composite biomarker indices such as the neutrophil-to-lymphocyte ratio, and a broad set of triggers has been proposed, ranging from senescent-cell accumulation and mitochondrial dysfunction to altered gut-barrier integrity and dysbiosis. Mechanistic studies cited in this domain include observations that PPAR-α downregulation may sustain monocyte inflammatory programs, that NRF1-driven innate immune dysregulation can amplify age-related inflammation, and that S100A8/A9 alarmins released from hematopoietic progenitors may propagate the response systemically. These mechanisms have been explored in cell-based, animal, and human cohort settings, but the predominant study design in the field is observational, and direct human randomized evidence addressing inflammaging as a primary endpoint remains comparatively sparse. Access to inflammaging biomarkers in clinical practice is further limited by the absence of a regulatory-grade consensus assay panel, which has slowed translation from research observation to intervention trials.", "claim_id": "claim_9"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "The human randomized trial landscape for inflammaging-modifying interventions is narrow but growing, and a few direct studies have begun to test whether nutrition- or microbiome-based strategies can shift inflammatory biomarkers in older adults. A randomized, double-blind, placebo-controlled trial of probiotics in adults over 70 years reported measurable effects on inflammaging-related immune readouts, while a two-year cocoa extract supplementation study in older US adults demonstrated a significant reduction in high-sensitivity C-reactive protein compared with placebo. Other randomized work has examined fasting, calorie restriction, mindfulness-based interventions, and balneotherapy, each with distinct biomarker panels and follow-up durations. Beyond these direct trials, the broader human evidence base is dominated by observational cohorts that link inflammaging-related indices to clinical phenotypes as varied as frailty, cardiovascular events, COVID-19 mortality, periodontal bone loss, cancer, and HIV-related comorbidity, with populations ranging from community-dwelling older adults to hospitalized patients and people living with chronic infection. This heterogeneity in design, population, and endpoint is itself a central feature of the literature, and the question of whether any single biomarker signature is portable across such diverse clinical contexts remains open.", "claim_id": "claim_10"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Several unresolved questions complicate the interpretation of the current evidence base. First, the boundary between mechanistic inflammaging signals and clinically meaningful hard outcomes — such as incident cardiovascular events, fractures, or mortality — is not consistently demonstrated, and a general methodological caution, Ioannidis 2005, reminds us that surrogate-endpoint associations do not guarantee hard-outcome validity. Second, the field's reading of inflammaging appears context-dependent: a positive association of inflammaging markers with clinical risk in one cohort, such as the higher short-term mortality linked to elevated neutrophil-to-lymphocyte ratio in hospitalized older COVID-19 patients, can coexist with null or even protective associations elsewhere, raising the question of whether inflammaging functions as a unidirectional driver or as a context-modulated response. Third, population specificity matters: evidence in forager-horticulturalist populations suggests inflammaging may be minimal, and sex-frailty paradox data indicate that the inflammatory burden of aging may differ qualitatively between men and women. Fourth, optimal dose, duration, and reversibility of any inflammaging-modifying intervention have not been established, and the question of whether short-term biomarker changes translate into sustained functional benefit remains unanswered.", "claim_id": "claim_11"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "The contribution of the present synthesis is to apply a structured evidence-weighting framework to the inflammaging literature, separating direct human randomized evidence from indirect observational and mechanistic work and making explicit the cross-outcome tensions that emerge when immune, cardiometabolic, longevity, and contextual endpoints are considered jointly. Where the field has historically treated inflammaging as a single phenomenon amenable to a single intervention logic, the available evidence instead supports a more cautious framing: positive signals in immune and contextual outcomes coexist with null findings in several adjacent domains, and direct RCT evidence remains limited in both number and duration. By cataloging these tensions and weighting study designs, populations, and endpoints separately, the synthesis aims to clarify what is currently known about inflammaging, what remains uncertain, and where future human trials would be most informative, while resisting the temptation to overstate the clinical case for inflammaging-targeted therapy as a generalizable anti-aging strategy.", "claim_id": "claim_12"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "The background evidence for Chronic low-grade inflammation is heterogeneous rather than uniformly confirmatory. Direct clinical sources such as Lazou-Ahren 2024, Li 2025b are interpreted separately from mechanistic studies such as Netti 2026, Lin 2025, Aitella 2025, because these evidence roles answer different questions about aging biology and clinical translation.", "claim_id": "claim_13"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "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.", "claim_id": "claim_14"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Across the retained sources, positive signals cluster around the immune and inflammation, contextual adjacent evidence outcome classes; null signals around the contextual adjacent evidence, immune and inflammation, longevity outcome classes; and negative or adverse signals around the immune and inflammation, longevity outcome classes. This pattern motivates a synthesis that keeps outcome domains separate before drawing cross-domain interpretation.", "claim_id": "claim_15"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "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.", "claim_id": "claim_16"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "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.", "claim_id": "claim_17"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "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.", "claim_id": "claim_18"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "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.", "claim_id": "claim_19"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, cognitive, contextual adjacent evidence, immune and inflammation, longevity, mechanism, mortality and survival, safety and comorbidity, skeletal, fracture, and bone); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.", "claim_id": "claim_20"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "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.", "claim_id": "claim_21"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "claim_id": "claim_22"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "| Contextual Adjacent Evidence | n=25; claims=804 | no extracted directional signal in 21/25 sources | 24 indirect; 1 review | limited corpus depth in this outcome class |", "claim_id": "claim_23"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "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.", "claim_id": "claim_24"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Contextual Adjacent Evidence: n=25; claims=804; no extracted directional signal in 21/25 sources | directness: 24 indirect; 1 review; main limitation: no direct clinical anchor.", "claim_id": "claim_25"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Additional corpus sources included animal/preclinical evidence; three sources populate the cardiometabolic outcome class, and none are positioned as a direct anti-aging clinical RCT in healthy adults. Cares 2026 is a systematic review of diet and exercise interventions in pediatric cancer survivors, framed around cardiometabolic disease risk and inflammaging biomarkers rather than longevity endpoints. Tizazu 2024 is an observational cohort in adults (canonical trial ID NCT03340935) examining how fasting and calorie restriction modulate age-associated immunosenescence and inflammaging. Xiong 2025 is a mechanistic cohort study in adults using advanced glycation end products to induce inflammaging in periodontal ligament fibroblasts via the RAGE/AKT/mTOR/glycolysis pathway. Across the corpus, the cardiometabolic evidence base combines a pediatric-survivor review, an adult fasting cohort, and a tissue-level mechanistic study, with no single trial anchoring a clinical inflammaging endpoint.", "claim_id": "claim_26"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Additional corpus sources included animal/preclinical evidence; the quantitative yield is uneven across the three sources. Cares 2026 reports no p-values in the available excerpt, consistent with a narrative table-driven systematic review. No effect direction is recorded for Cares 2026 or Xiong 2025, and the effect direction for Tizazu 2024 is listed as unclear, so the cardiometabolic class as currently curated cannot support a directional synthesis statement.", "claim_id": "claim_27"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Mechanistically, the cardiometabolic sources converge on inflammaging-relevant pathways even though the populations and exposures differ. Preclinical data from Xiong 2025 place the RAGE/AKT/mTOR/glycolysis axis in periodontal ligament fibroblasts, identifying a tissue substrate through which advanced glycation end products could propagate chronic inflammatory signaling relevant to cardiometabolic risk. Mechanistic human and observational data from Tizazu 2024 point to dendritic-cell compartment remodeling (mDCs versus pDCs) under fasting/calorie restriction, linking nutrient-sensing inputs to immunosenescence biomarkers. The Cares 2026 review layer sits above these mechanistic findings by aggregating diet-and-exercise interventions in a pediatric survivor population, where the same downstream inflammatory biomarkers are framed as cardiometabolic risk markers rather than as longevity endpoints.", "claim_id": "claim_28"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "Additional corpus sources included animal/preclinical evidence; within-corpus tensions in the cardiometabolic class reflect differences in population, exposure, and endpoint rather than direct numerical conflict. Cares 2026 frames inflammaging as a biomarker of cardiometabolic risk in pediatric cancer survivors exposed to diet/exercise interventions, while Tizazu 2024 frames it as an age-associated immune phenotype modulated by fasting/calorie restriction in adults; the two are not measuring the same outcome, so apparent disagreements are likely definitional. Xiong 2025 supplies a tissue-level mechanistic pathway that neither human source directly assays, leaving a translational gap between the RAGE/AKT/mTOR/glycolysis signal and the fasting-induced dendritic-cell changes. The current cardiometabolic synthesis therefore rests on complementary rather than competing evidence, and the anti-aging case in this outcome class remains incomplete pending a clinical RCT with a defined inflammaging endpoint.", "claim_id": "claim_29"}, {"candidate_sources": [{"doi": "10.3390/antiox11122413", "study": "Doxycycline Attenuated Ethanol-Induced Inflammaging in Endothelial Cells: Implications in Alcohol-Mediated Vascular Diseases", "url": "https://doi.org/10.3390/antiox11122413"}, {"doi": "10.1007/s00345-024-05409-z", "study": "Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation", "url": "https://doi.org/10.1007/s00345-024-05409-z"}, {"doi": "10.3390/antiox15050599", "study": "Morin and Morin Semicarbazone Combined with Fucoxanthin Have Potential Anti-Inflammaging Effects Through Modulation of Nrf2/HO-1 System in UVB-Exposed HaCaT Keratinocytes", "url": "https://doi.org/10.3390/antiox15050599"}, {"doi": "10.1186/s12979-025-00548-2", "study": "Neutrophil-to-lymphocyte ratio as a sex-specific predictor of short-term mortality in hospitalised older adults with COVID-19: a pragmatic biomarker of inflammaging in acute vulnerability", "url": "https://doi.org/10.1186/s12979-025-00548-2"}, {"doi": "10.1002/ajpa.70211", "study": "Minimal Evidence of Inflammaging in Naturalistic Chimpanzee Populations", "url": "https://doi.org/10.1002/ajpa.70211"}], "claim": "The cognitive evidence base in the curated inflammaging corpus is anchored by Aitella 2025, a mechanistic preclinical study framing rheumatoid arthritis and osteoporosis as prototypes of immunosenescence within osteoimmunology and detailing molecular pathways of inflammaging alongside targeted therapeutic strategies. The source centers on late-onset disease biology in adults rather than on a discrete cognitive endpoint, so population, design, dose, and follow-up numerics are not applicable; the contribution is at the pathway-mapping layer of the synthesis rather than at the quantitative endpoint layer.", "claim_id": "claim_30"}]}
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