source · application/json
source_f7ff2af580c949f8
sha256 dc4b3b97f5d1d403ac1ae512b4a371a9a065296281b1c94a9c1ccb8b349f8ccd
by researka:v2 · 2026-06-23 08:26:01.151580+04:00
{"content_hash": "sha256:24b09388eccfb1eee347273a3bbd8ed1c19934abfff799cefa1917cfc63e20bd", "edges": [{"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_1", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_2", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_3", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_4", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_5", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_6", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_7", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_8", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_9", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_10", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_11", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_12", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_13", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_14", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_15", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_16", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_17", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_18", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_19", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_20", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_21", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_22", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_23", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_24", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_25", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_26", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_27", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_28", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_29", "type": "contains_claim"}, {"from": "bd88fdac-646d-49da-ad47-a3e928cc057a", "to": "claim_30", "type": "contains_claim"}], "nodes": [{"id": "bd88fdac-646d-49da-ad47-a3e928cc057a", "title": "Hypothesis-Generating Brief: Immune senescence — full paper", "type": "publication"}, {"id": "claim_1", "text": "This paper synthesizes evidence on Immune senescence across 46 accepted source papers and 750 high-confidence extracted claims.", "type": "claim"}, {"id": "claim_2", "text": "The evidence profile contains 2 direct clinical sources, 41 adjacent clinical sources, and 3 mechanistic or model-system sources, with 96 cross-study disagreements across the evidence base.", "type": "claim"}, {"id": "claim_3", "text": "Positive study-level signals are summarized in the immune and inflammation outcome class, null signals in the contextual adjacent evidence, immune and inflammation, longevity outcome classes, and negative signals in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "type": "claim"}, {"id": "claim_4", "text": "The conclusion is that Immune senescence 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_5", "text": "This manuscript is reported as a Evidence brief. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-immunosenescence-v06-DAILY-2026-06-23T04-08-56Z`.", "type": "claim"}, {"id": "claim_6", "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_7", "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_8", "text": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, cognitive, contextual adjacent evidence, frailty, immune and inflammation, longevity, safety and comorbidity); 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_9", "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_10", "text": "Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.", "type": "claim"}, {"id": "claim_11", "text": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "type": "claim"}, {"id": "claim_12", "text": "| Contextual Adjacent Evidence | n=18; claims=286 | no extracted directional signal in 18/18 sources | 16 indirect; 2 review | limited corpus depth in this outcome class |", "type": "claim"}, {"id": "claim_13", "text": "This evidence brief reports outcome packets as a map of retained evidence rather than as a full journal Results narrative or pooled effect estimate.", "type": "claim"}, {"id": "claim_14", "text": "18 included sources were assigned to this outcome class. Directional coding: null=18. Directness coding: indirect=16, review=2.", "type": "claim"}, {"id": "claim_15", "text": "15 included sources were assigned to this outcome class. Directional coding: null=11, positive=1, unclear=3. Directness coding: direct=1, indirect=12, mechanistic=2.", "type": "claim"}, {"id": "claim_16", "text": "3 included sources were assigned to this outcome class. Directional coding: null=3. Directness coding: indirect=3.", "type": "claim"}, {"id": "claim_17", "text": "Evidence for this outcome class is represented in the structured results table, but the retained narrative paragraphs were more strongly assigned to adjacent outcome classes. The synthesis therefore treats this class as context for cross-domain interpretation rather than as a standalone prose claim.", "type": "claim"}, {"id": "claim_18", "text": "4 included sources were assigned to this outcome class. Directional coding: null=3, unclear=1. Directness coding: indirect=4.", "type": "claim"}, {"id": "claim_19", "text": "2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: indirect=2.", "type": "claim"}, {"id": "claim_20", "text": "2 included sources were assigned to this outcome class. Directional coding: null=2. Directness coding: direct=1, indirect=1.", "type": "claim"}, {"id": "claim_21", "text": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: mechanistic=1.", "type": "claim"}, {"id": "claim_22", "text": "1 included source were assigned to this outcome class. Directional coding: null=1. Directness coding: indirect=1.", "type": "claim"}, {"id": "claim_23", "text": "Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.", "type": "claim"}, {"id": "claim_24", "text": "The corpus contains no long-term, hard-outcome randomized trial in non-diabetic older adults, and the absence of such evidence is a primary boundary on every cross-domain inference. Ioannidis 2005 underscores the risk that surrogate-endpoint RCTs in this corpus (e. For example, Rastgoo 2025's senescent-cell and SA-β-gal readouts) may not translate to clinical benefit, and that caveat applies to most of the headline conclusions.", "type": "claim"}, {"id": "claim_25", "text": "Several clinically prominent outcomes are touched by only a single source, so any conclusion that names those outcomes cannot be replicated inside the corpus. The lymphocyte-to-monocyte ratio / HFpEF longevity signal rests on Cai 2026 alone; the BC02-adjuvanted VZV-gE vaccine claim of overcoming age-related immune limitation rests on Li 2026 alone; the senolytic Agrimonia pilosa pilot in middle-aged humans rests on Shimizu 2025 alone; and the centenarian immune-profiling data rest on Anaya 2026. When a single observational cohort or preclinical study is the entire evidence base for a claim, the point estimate carries an unreplicated, design-specific uncertainty, and the synthesis cannot adjudicate between chance, confounding, and a true effect. The -type null vs positive tension on the immune outcome class (Lee 2025 positive vs. Khoury 2025 / Cevirgel 2025 / Coelho 2025 / Fragkou 2026 / Anaya 2026 null) compounds this risk, because there is no within-corpus independent dataset that resolves which direction generalizes.", "type": "claim"}, {"id": "claim_26", "text": "Additional corpus sources included animal/preclinical evidence; external validity is bounded by the populations the trials and cohorts actually enrolled. Geographically, the corpus is concentrated in Chinese (Xiao 2023, Chen 2026, Li 2026, Li 2026b, Zhong 2025, Zhang 2026, Zhang 2024, He 2025, Reina-Alfonso 2026), Brazilian (Ventura 2025, Coelho 2025, Dema 2025, Francavilla 2025), and Bulgarian (Nikolova 2025) cohorts, with single-country representation from Colombia (Anaya 2026) and Italy (Valentino 2024, Aitella 2025, Aitella 2026).", "type": "claim"}, {"id": "claim_27", "text": "Several clinically actionable claims are supported only by mechanistic or preclinical evidence, with no within-corpus human-RCT bridge. Lee 2025 reports a positive in-vitro T-cell mitochondrial effect, but is not an in-human trial of clinical benefit. Without a within-corpus human RCT that tests a mechanistically nominated intervention on a hard endpoint, the immunosenescence anti-aging case as currently constituted remains incomplete, and the boundary conditions for translation — age stratum, comorbidity profile, baseline immune fitness — are not established by the available evidence.", "type": "claim"}, {"id": "claim_28", "text": "For Immune senescence, the final interpretation is deliberately tiered: the retained clinical and mechanistic evidence profile defines a bounded geroscience rationale, but the corpus does not support treating mechanistic target engagement, intermediate biomarkers, and patient-relevant outcomes as interchangeable evidence. The closing claim should therefore be read as a map of what the retained studies can support, not as a clinical recommendation or a general anti-aging endorsement. Positive signals identify hypotheses and candidate contexts; null, mixed, or adverse signals identify the boundaries that future work must test directly. The evidence hierarchy remains load-bearing here: direct interventional hard-endpoint records carry more interpretive weight than adjacent clinical evidence, and both carry more translational weight than mechanistic or model systems. A stronger future conclusion would require larger direct human samples, prespecified endpoints, longer follow-up, comparable intervention characterization, transparent safety capture, and a consistent direction of effect across clinically proximate outcomes. Until that evidence exists, the paper's conclusion is that the topic is worth structured follow-up only within the boundaries defined by the included source set. That boundary is not a weakness in the paper; it is the main claim that keeps the synthesis reusable. Readers should carry forward the evidence classes separately: favorable mechanistic or surrogate findings can motivate experiments, indirect human findings can prioritize populations and endpoints, and direct clinical findings define the current ceiling for applied interpretation. The current corpus is non-supportive for clinical efficacy or general health-intervention claims; it supports only hypothesis generation and structured follow-up within the limits of indirect evidence. Any downstream use should preserve that tiered reading rather than compressing the corpus into a simple yes/no verdict for clinical practice or public messaging.", "type": "claim"}, {"id": "claim_29", "text": "This synthesis maps 46 included sources on Immunosenescence across 8 outcome classes and 96 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.", "type": "claim"}, {"id": "claim_30", "text": "Across 46 curated reference papers, the evidence base for immunosenescence shows a context-dependent profile. Positive signals appear in: immune. Null findings dominate: contextual other. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The immunosenescence anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established.", "type": "claim"}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12979-023-00364-6", "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": "Immunogenicity and safety of quadrivalent influenza vaccine among young and older adults in Tianjin, China: implication of immunosenescence as a risk factor", "type": "source", "url": "https://doi.org/10.1186/s12979-023-00364-6", "year": 2023}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12979-026-00560-0", "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": "Kaempferol alleviates T-cell immunosenescence and inflammaging in aged mice via the SIRT3-LKB1-AMPK-mitophagy pathway", "type": "source", "url": "https://doi.org/10.1186/s12979-026-00560-0", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1080/21645515.2026.2617728", "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": "BC02-adjuvanted varicella-zoster virus glycoprotein E subunit vaccine overcomes immunosenescence to induce robust neutralizing antibodies and multifunctional T-cell immunity in seropositive aged murine models", "type": "source", "url": "https://doi.org/10.1080/21645515.2026.2617728", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.xcrm.2025.102484", "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": "Physical activity decreases cancer burden by alleviating immunosenescence-related inflammation and improving overall immunity", "type": "source", "url": "https://doi.org/10.1016/j.xcrm.2025.102484", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/diseases14010026", "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": "Predictors of Severe Herpes Zoster: Contributions of Immunosenescence, Metabolic Risk, and Lifestyle Behaviors", "type": "source", "url": "https://doi.org/10.3390/diseases14010026", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1038/s41514-026-00340-6", "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": "Biological age and immunosenescence in Colombian centenarians", "type": "source", "url": "https://doi.org/10.1038/s41514-026-00340-6", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/acel.70077", "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": "Immunosenescence Profile Is Associated With Increased Susceptibility to Severe COVID ‐19", "type": "source", "url": "https://doi.org/10.1111/acel.70077", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/agm2.12342", "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": "Fasting and calorie restriction modulate age‐associated immunosenescence and inflammaging", "type": "source", "url": "https://doi.org/10.1002/agm2.12342", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1007/s11102-025-01632-y", "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": "The impact of growth hormone (GH) on immunosenescence: exploring the role of B and T cells", "type": "source", "url": "https://doi.org/10.1007/s11102-025-01632-y", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/nu17040667", "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": "Preliminary Data on the Senolytic Effects of Agrimonia pilosa Ledeb. Extract Containing Agrimols for Immunosenescence in Middle-Aged Humans: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Study", "type": "source", "url": "https://doi.org/10.3390/nu17040667", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12979-025-00504-0", "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": "CD31 + naïve T cells associate with immunosenescence and responsiveness to multiple vaccines in older adults", "type": "source", "url": "https://doi.org/10.1186/s12979-025-00504-0", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fimmu.2025.1570441", "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": "Co-administration of vitamin D and N-acetylcysteine to modulate immunosenescence in older adults with vitamin D deficiency: a randomized clinical trial", "type": "source", "url": "https://doi.org/10.3389/fimmu.2025.1570441", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fmed.2026.1729112", "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": "Age-related changes in circulating immune factors reveal biomarkers of immunosenescence", "type": "source", "url": "https://doi.org/10.3389/fmed.2026.1729112", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fimmu.2025.1547854", "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": "Living in endemic area for infectious diseases is associated to differences in immunosenescence and inflammatory signatures", "type": "source", "url": "https://doi.org/10.3389/fimmu.2025.1547854", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12979-024-00491-8", "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": "Differential associations of anti-cytomegalovirus antibodies and soluble CD14 levels with immunosenescence in people living with HIV on long term antiretroviral therapy", "type": "source", "url": "https://doi.org/10.1186/s12979-024-00491-8", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1093/gerona/glag095", "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": "Immunosenescence and cytomegalovirus-associated immune signatures on severe acute respiratory syndrome coronavirus 2 booster responses", "type": "source", "url": "https://doi.org/10.1093/gerona/glag095", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1002/advs.202407398", "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": "MAM‐STAT3‐Driven Mitochondrial Ca +2 Upregulation Contributes to Immunosenescence in Type A Mandibuloacral Dysplasia Patients", "type": "source", "url": "https://doi.org/10.1002/advs.202407398", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12979-025-00506-y", "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": "Enhancing flu vaccine responses in older adults: preliminary insights from the ISOLDA study on immunosenescence and antioxidant and anti-inflammatory approaches", "type": "source", "url": "https://doi.org/10.1186/s12979-025-00506-y", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.31083/RCM45403", "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": "Lymphocyte-To-Monocyte Ratio is Partially Mediated in Age-Related Cardiovascular Mortality in HFpEF: Immunosenescence, Inflamm-Aging, and Longevity", "type": "source", "url": "https://doi.org/10.31083/RCM45403", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12979-022-00309-5", "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": "Aging, inflammaging and immunosenescence as risk factors of severe COVID-19", "type": "source", "url": "https://doi.org/10.1186/s12979-022-00309-5", "year": 2022}, {"comparator": "not extracted", "directness": "review-level", "doi": "10.3389/fnagi.2026.1776458", "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": "Immunosenescence and its impact on ischemic stroke risk and outcomes in older adults: a systematic review", "type": "source", "url": "https://doi.org/10.3389/fnagi.2026.1776458", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12906-024-04732-7", "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": "A randomized controlled trial to assess the efficacy of standardized tai chi in prefrail older adults with immunosenescence: design and protocol", "type": "source", "url": "https://doi.org/10.1186/s12906-024-04732-7", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/acel.14491", "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": "Disease Aggravation With Age in an Experimental Model of Multiple Sclerosis: Role of Immunosenescence", "type": "source", "url": "https://doi.org/10.1111/acel.14491", "year": 2025}, {"comparator": "not 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"directness": "review-level", "doi": "10.21037/atm-22-4405", "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": "Immunosenescence is a therapeutic target for frailty in older adults: a narrative review", "type": "source", "url": "https://doi.org/10.21037/atm-22-4405", "year": 2022}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1111/acel.70548", "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": "Immunosenescence and Vaccine Efficacy in Aging: Dynamic Interplay of Gut Microbiota and mTOR Signaling Pathways", "type": "source", "url": "https://doi.org/10.1111/acel.70548", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12915-025-02484-5", "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": "Aging-associated transcriptional programs in T cells signify constituents of TGF-β signaling for immunosenescence", "type": "source", "url": "https://doi.org/10.1186/s12915-025-02484-5", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms26031258", "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": "Markers of Type 2 Inflammation and Immunosenescence Are Upregulated in Localized Scleroderma", "type": "source", "url": "https://doi.org/10.3390/ijms26031258", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": 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"endpoint": "not extracted", "id": "source_32", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "HIV infection and immunosenescence: challenges and intervention strategies", "type": "source", "url": "https://doi.org/10.1186/s12916-025-04545-6", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fimmu.2026.1792954", "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": "Bridging aging and colorectal cancer: synergistic roles of inflammaging and immunosenescence", "type": "source", "url": "https://doi.org/10.3389/fimmu.2026.1792954", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1016/j.jgr.2025.05.004", "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": "Red ginseng extract enhances mitochondrial function and alleviates immunosenescence in T cells", "type": "source", "url": "https://doi.org/10.1016/j.jgr.2025.05.004", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/microorganisms12102052", "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": "Immunosenescence: How Aging Increases Susceptibility to Bacterial Infections and Virulence Factors", "type": "source", "url": "https://doi.org/10.3390/microorganisms12102052", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fragi.2024.1490302", "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": "The 3 I’s of immunity and aging: immunosenescence, inflammaging, and immune resilience", "type": "source", "url": "https://doi.org/10.3389/fragi.2024.1490302", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms27031206", "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": "Immunosenescence and Allergy: Molecular and Cellular Links Between Inflammaging, Neuro-Immune Aging, and Response to Biologic Therapies", "type": "source", "url": "https://doi.org/10.3390/ijms27031206", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1183/16000617.0248-2025", "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": "Immunosenescence and susceptibility to respiratory viruses: a state-of-the-art review", "type": "source", "url": "https://doi.org/10.1183/16000617.0248-2025", "year": 2026}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fragi.2025.1568034", "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": "Multivariate analysis of immunosenescence data in healthy humans and diverse diseases", "type": "source", "url": "https://doi.org/10.3389/fragi.2025.1568034", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fonc.2025.1567896", "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": "Nanoparticle-mediated delivery of herbal-derived natural products to modulate immunosenescence-induced drug resistance in cancer therapy: a comprehensive review", "type": "source", "url": "https://doi.org/10.3389/fonc.2025.1567896", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3390/ijms26199268", "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": "Rheumatoid Arthritis and Osteoporosis as Prototypes of Immunosenescence in Osteoimmunology: Molecular Pathways of Inflammaging and Targeted Therapies", "type": "source", "url": "https://doi.org/10.3390/ijms26199268", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fimmu.2025.1660874", "effect": "not 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"id": "source_44", "intervention_or_exposure": "not extracted", "population": "not extracted", "risk_of_bias": "not appraised in public sidecar", "study": "“Immunopause” no more: exercise to counter immunosenescence in aging", "type": "source", "url": "https://doi.org/10.1186/s12979-025-00549-1", "year": 2025}, {"comparator": "not extracted", "directness": "primary", "doi": "10.3389/fimmu.2024.1375730", "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": "Impact and potential value of immunosenescence on solid gastrointestinal tumors", "type": "source", "url": "https://doi.org/10.3389/fimmu.2024.1375730", "year": 2024}, {"comparator": "not extracted", "directness": "primary", "doi": "10.1186/s12979-024-00489-2", "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": "The role of autoantibodies in bridging obesity, aging, and immunosenescence", "type": "source", "url": "https://doi.org/10.1186/s12979-024-00489-2", "year": 2024}, {"comparator": "not extracted", "directness": "citation", "doi": null, "effect": "not extracted", "endpoint": "not extracted", "id": "source_47", "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_48", "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_49", "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_50", "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_51", "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": "bd88fdac-646d-49da-ad47-a3e928cc057a", "screening": {"excluded": 0, "exclusion_reasons": ["No PRISMA full-text exclusion-stage filter was applied."], "flow": ["identified", "screened", "excluded_with_reasons", "included"], "identified": 46, "included": 46, "included_or_retained": 46, "screened": 46, "wording": "46 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit."}}
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