{"publication_id":"eff2808f-cded-4bcd-b7a5-59a823b84f7b","screening":{"identified":53,"screened":53,"excluded":0,"included":53,"included_or_retained":53,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"53 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted evidence map, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["The conclusion is that Alpha-ketoglutarate remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.","4 included sources were assigned to this outcome class. Directional coding: mixed=1, null=3. Directness coding: mechanistic=4.","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.","Finally, the corpus contains a mechanism-to-clinic gap for the most clinically relevant claim, namely that αKG influences cardiovascular, skeletal, and longevity outcomes in humans. Mechanistic plausibility is densely documented: PI3K/Akt/HIF-1α angiogenesis in skin flaps (Huang 2025), PHD1-dependent NF-κB suppression in osteoclastogenesis (Tian 2023b), epigenetic H3K27me3 reduction in periodontal regeneration (Hasegawa 2026), histone methylation rescue in age-related osteoporosis (Wang 2020), and Tnfrsf12a/Fn14 histone-modification protection against cancer cachexia (Ruiz 2023). However, each of these sources is either preclinical (An 2021, Iwaniak 2022, Bayliak 2017, Kalawaj 2020), mechanistic-only (Iniguez 2022, Cai 2016, Qiu 2025, Sekita 2021, Wu 2018, Burdyliuk 2017, Showalter 2017, Fiehn 2016), or review/protocol-level (Sandalova 2023, Lamichhane 2023, Doroftei 2024, Wu 2016). 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. Pending further trials, the intervention should not be used off-label for geroprotection or anti-aging purposes outside clinical-trial settings given current 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.","Across 53 curated reference papers, the evidence base for Alpha shows a context-dependent profile. Positive signals appear in: safety comorbidity. Null findings dominate: contextual other, cardiometabolic. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Alpha 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."]}