source · application/json
source_3564a3ce4db348e4
sha256 f2ecec435b62649909a6593e2b9568f21e5ddbd794f97545b203f9032e764f32
by researka:v2 · 2026-05-28 07:55:06.788921+04:00
{"publication_id": "ff0598d5-47d1-45bf-91bb-ff8e74948493", "traces": [{"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "What does the current evidence establish about Allostatic Load and human geroscience? This synthesis tests the thesis that evidence for Allostatic load is context-dependent, separating outcome-specific signals from broader claims and identifying the evidence gaps that should bound interpretation. Allostatic load (AL) reflects cumulative biological burden from chronic stress exposure, yet its anti-aging promise remains unsettled across human and preclinical domains. To adjudicate this tension, we conducted an AI-assisted structured evidence synthesis with full audit trail, integrating 50 curated references across mechanistic and clinical outcomes. In human trials, creatine plus β-hydroxy-β-methylbutyrate preserved glutathione redox balance in older adults (P < 0.05), aligning with mechanistic expectations, though effect direction remains unclear. Cardiometabolic outcomes similarly show null findings, including in polycystic ovary syndrome trials where combined training did not improve metabolic biomarkers. Across cross-study disagreements identified, mechanistic plausibility coexists with mixed or sparse human-RCT evidence, underscoring the boundary conditions of AL interventions. Across the corpus, the evidence supports a model where mechanistic plausibility is strongest in preclinical contexts, while human applicability remains contingent on outcome class and intervention specificity. Critical gaps include the lack of harmonized AL indices in clinical trials an", "claim_id": "claim_1"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "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.", "claim_id": "claim_2"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.", "claim_id": "claim_3"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, dosing and pharmacokinetics, immune, longevity, mortality and survival, 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.", "claim_id": "claim_4"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "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_5"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence.", "claim_id": "claim_6"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "| Contextual Adjacent Evidence | n=23; claims=1056 | null signal in 15/23 sources | 13 indirect; 2 mechanistic; 8 review | limited corpus depth in this outcome class |", "claim_id": "claim_7"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "| Immune | n=9; claims=679 | null signal in 5/9 sources | 2 direct; 3 indirect; 4 review | limited corpus depth in this outcome class |", "claim_id": "claim_8"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "| Cardiometabolic | n=4; claims=274 | null signal in 3/4 sources | 1 direct; 1 indirect; 2 review | limited corpus depth in this outcome class |", "claim_id": "claim_9"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "| Dosing and Pharmacokinetics | n=4; claims=219 | null signal in 4/4 sources | 4 review | limited corpus depth in this outcome class |", "claim_id": "claim_10"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "| Deficiency Prevalence | n=1; claims=113 | null signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |", "claim_id": "claim_11"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "| Mortality and Survival | n=1; claims=29 | null signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |", "claim_id": "claim_12"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "| Safety and Comorbidity | n=1; claims=156 | null signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |", "claim_id": "claim_13"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "The retained allostatic load corpus is reported by outcome class before any cross-domain interpretation. This structure prevents favorable, null, mixed, and adverse evidence from being blended across biologically different endpoints.", "claim_id": "claim_14"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "The contextual adjacent evidence packet includes 23 source-level summaries and 1056 high-confidence observations. Directional coding within this packet is negative=3, null=15, positive=2, unclear=3, and directness coding is indirect=13, mechanistic=2, review=8. These counts describe the frozen evidence state for this outcome, not a pooled treatment estimate.", "claim_id": "claim_15"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Additional corpus sources included animal/preclinical evidence; representative sources include Fan 2023, Quinn 2022, Nikrad 2023. This outcome is interpreted within its own packet first; any broader synthesis is deferred until the cross-domain section so that the writer cannot merge evidence from unrelated outcome classes.", "claim_id": "claim_16"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "The immune evidence packet includes 9 source-level summaries and 679 high-confidence observations. Directional coding within this packet is mixed=1, null=5, positive=1, unclear=2, and directness coding is direct=2, indirect=3, review=4.", "claim_id": "claim_17"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Directional coding within this packet is negative=1, null=3, unclear=3, and directness coding is indirect=3, review=4.", "claim_id": "claim_18"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Directional coding within this packet is null=3, unclear=1, and directness coding is direct=1, indirect=1, review=2.", "claim_id": "claim_19"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Directional coding within this packet is null=4, and directness coding is review=4.", "claim_id": "claim_20"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Directional coding within this packet is null=1, and directness coding is indirect=1.", "claim_id": "claim_21"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Descriptive findings remain separate from interpretation and endpoint-specific boundaries. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation", "claim_id": "claim_22"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Longevity is retained as a separate Results slice (n=7; null signal in 3/7 sources; 3 indirect; no direct clinical anchor) and is not pooled into adjacent endpoint classes.", "claim_id": "claim_23"}, {"candidate_sources": [{"doi": "10.1007/s10522-026-10407-2", "study": "Ramos-Hernandez 2026", "url": "https://doi.org/10.1007/s10522-026-10407-2"}, {"doi": "10.1111/1747-0080.12672", "study": "Giang 2021", "url": "https://doi.org/10.1111/1747-0080.12672"}, {"doi": "10.1186/s12902-024-01793-0", "study": "Nasiri 2025", "url": "https://doi.org/10.1186/s12902-024-01793-0"}, {"doi": "10.18632/aging.206235", "study": "Moel 2025", "url": "https://doi.org/10.18632/aging.206235"}, {"doi": "10.14814/phy2.70390", "study": "Lee 2025", "url": "https://doi.org/10.14814/phy2.70390"}], "claim": "Cardiometabolic is retained as a separate Results slice (n=4; 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