source · application/json
source_566a3e0199dd439c
sha256 5c030003f40facecbc4721ddac5fad436a9f962ab9d47ee8c6f0db40905729ed
by researka:v2 · 2026-06-20 16:56:32.770878+04:00
{"publication_id": "f7b01234-38e2-4b03-b28b-707000e0635b", "traces": [{"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "Evidence-honesty note: 16/16 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.", "claim_id": "claim_1"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "This paper synthesizes evidence on Epigenome editing longevity across 16 included source papers and 279 high-confidence extracted claims.", "claim_id": "claim_2"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 15 adjacent clinical sources, and 1 mechanistic or model-system source, with 0 cross-study disagreements across the evidence base.", "claim_id": "claim_3"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "No single positive outcome class dominates the retained corpus; null signals cluster in the contextual adjacent evidence and mechanism outcome classes, and negative signals cluster in no dominant outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.", "claim_id": "claim_4"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "The conclusion is that Epigenome editing longevity should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.", "claim_id": "claim_5"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "This manuscript is reported as a Thin-corpus 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-epigenome_editing_longevity-v06-DAILY-2026-06-20T12-44-52Z`.", "claim_id": "claim_6"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "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 appraisal, and claim registry) rather than from re-parsed full text.", "claim_id": "claim_7"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "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).", "claim_id": "claim_8"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "Evidence-tension synthesis: claims grouped by outcome class (contextual adjacent evidence, mechanism); 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_9"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "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_10"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "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_11"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |", "claim_id": "claim_12"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "| Contextual Adjacent Evidence | n=15; claims=272 | no extracted directional signal in 15/15 sources | 15 indirect | limited corpus depth in this outcome class |", "claim_id": "claim_13"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "The retained Epigenome editing longevity 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": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "The contextual adjacent evidence evidence packet includes 15 source-level summaries and 272 high-confidence observations. Directional coding within this packet is null=15, and directness coding is indirect=15. These counts describe the frozen evidence state for this outcome, not a pooled treatment estimate.", "claim_id": "claim_15"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "Additional corpus sources included animal/preclinical evidence; representative sources: OGeen 2022, Li 2020, Swain 2023.", "claim_id": "claim_16"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "Across outcome classes, the manuscript treats disagreement as part of the evidence rather than as noise to smooth away. A null or adverse signal in one section does not cancel a favorable signal in another; it defines the boundary condition for interpretation.", "claim_id": "claim_17"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.", "claim_id": "claim_18"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "The curated corpus of 16 reference papers contains no long-term randomized clinical trial of an epigenome-editing intervention with a hard longevity endpoint such as all-cause mortality, incident frailty, or life expectancy in non-diabetic older adults. Consequently, the headline framing of the Epigenome case rests entirely on mechanistic plausibility rather than on the kind of evidence that would support a survival claim; the absence of a TAME-style or analogous mortality trial in this corpus is itself the most important limitation. The single most-cited surrogate-only concern is general: surrogate associations do not guarantee hard-outcome validity (Ioannidis 2005), and no source here resolves that concern for any editing construct.", "claim_id": "claim_19"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "Several clinically attractive outcomes are supported by a single source in the corpus and therefore cannot be replicated internally. With one source per claim, the within-corpus estimate of consistency is undefined rather than low, and any quantitative summary that aggregates across these single-study endpoints would overstate the evidence. The fragility is structural: removing any one of these sources deletes the only available human-cell data point for that endpoint.", "claim_id": "claim_20"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "The enrolled populations are narrowly defined and poorly matched to the target clinical audience. With the exception of Horii 2022, which uses mice, every source is labeled population: adults and derives its evidence from transformed cell lines (e. Translational relevance to humans remains uncertain.g., translational relevance to humans remains uncertain). External validity therefore ends at the cell-culture and rodent-model boundary: there is no source enrolling frail older adults, sarcopenic patients (Cruz-Jentoft 2019 cutoffs of 27 kg grip strength for men and 16 kg for women are not used as enrollment criteria in any study here), or populations characterized by gait speed (Studenski 2011 frailty threshold of 0.8 m/s; Cesari 2009 severe-mobility cutoff of 0.6 m/s).", "claim_id": "claim_21"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "The corpus does not measure the endpoints that would matter for a clinical longevity decision. None of these molecular p-values can be mapped onto a hard clinical endpoint, leaving the evidence base unable to bound effect sizes for outcomes clinicians or regulators would recognize.", "claim_id": "claim_22"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "For Epigenome editing longevity, the final interpretation is deliberately tiered: the retained clinical and adjacent 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.", "claim_id": "claim_23"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "This synthesis maps 16 included sources on Epigenome Editing Longevity across 2 outcome classes with no cross-study disagreements surfaced. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.", "claim_id": "claim_24"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "Across 16 curated reference papers, the evidence base for Epigenome editing shows a context-dependent profile. Null findings dominate: contextual other, mechanism. The Epigenome 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.", "claim_id": "claim_25"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.", "claim_id": "claim_26"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |", "claim_id": "claim_27"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "| contextual adjacent evidence | 0 | 15 | null | direct interventional hard-endpoint gap |", "claim_id": "claim_28"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "| P1 | mechanism: direct interventional hard-endpoint gap | 0 direct and 1 indirect source; direction profile: null |", "claim_id": "claim_29"}, {"candidate_sources": [{"doi": "10.1093/nar/gkac123", "study": "Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing", "url": "https://doi.org/10.1093/nar/gkac123"}, {"doi": "10.1038/s41467-020-14362-5", "study": "Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing", "url": "https://doi.org/10.1038/s41467-020-14362-5"}, {"doi": "10.1093/nar/gkad1108", "study": "A modular dCas9-based recruitment platform for combinatorial epigenome editing", "url": "https://doi.org/10.1093/nar/gkad1108"}, {"doi": "10.1093/hmg/ddab255", "study": "Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing", "url": "https://doi.org/10.1093/hmg/ddab255"}, {"doi": "10.1093/nar/gkae798", "study": "Chem-CRISPR/dCas9 FCPF : a platform for chemically induced epigenome editing", "url": "https://doi.org/10.1093/nar/gkae798"}], "claim": "| P2 | contextual adjacent evidence: direct interventional hard-endpoint gap | 0 direct and 15 indirect sources; 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