🧬 Aging Wiki

R8

61 min read

log/R8.md — Round 8 entries

Sub-file of log — see parent for index.

[2026-05-04] verify | cancer.md

Pages verified: 1

  • phenotypes/cancer.md — corrections: 8 substantive; verified: true (partial scope — Guevara-Aguirre 2011 and Vasan&Cantley 2022 unverifiable; no-fulltext-access retained on both)

Sources checked:

  • Hanahan & Weinberg 2011 (10.1016/j.cell.2011.02.013) — local PDF (downloaded this session); verified
  • Hanahan 2022 (10.1158/2159-8290.CD-21-1059) — local PDF (downloaded this session); verified
  • Tyner 2002 (10.1038/415045a) — local PDF; verified
  • Mendrysa 2006 (10.1101/gad.1378506) — local PDF; verified (INVERTED finding confirmed correct)
  • Ortega-Molina 2012 (10.1016/j.cmet.2012.02.001) — local PDF; verified
  • Garcia-Cao 2012 (10.1016/j.cell.2012.02.030) — local PDF; verified (no lifespan measurement confirmed)
  • Baker 2016 (10.1038/nature16932) — local PDF; verified
  • Jaiswal 2014 (10.1056/NEJMoa1408617) — local PDF; verified
  • Roberts 2016 (10.1056/nejmoa1513257) — local PDF; verified
  • Guevara-Aguirre 2011 (10.1126/scitranslmed.3001845) — download failed twice; no-fulltext-access
  • Vasan & Cantley 2022 (10.1038/s41571-022-00633-1) — download failed twice; no-fulltext-access

Corrections (substantive):

  1. Hallmarks section body WRONG ATTRIBUTION. Items 7-10 were labeled “Emerging hallmarks (2022)” but all four are from H&W 2011, not Hanahan 2022. Items 7-8 (deregulated energetics; avoiding immune destruction) are H&W 2011’s two new emerging hallmarks; items 9-10 (genome instability; tumor-promoting inflammation) are H&W 2011’s two enabling characteristics. Section restructured with correct H&W 2011 attribution for all four, and a separate section added for the four actual Hanahan 2022 new dimensions.
  2. Hanahan 2022 new dimensions WRONG in footnote. Wiki stated “adds 4 emerging hallmarks: deregulated cellular metabolism, immune evasion, epigenome reprogramming (revised), phenotypic plasticity.” Actual Hanahan 2022 additions are: (1) unlocking phenotypic plasticity, (2) nonmutational epigenetic reprogramming, (3) polymorphic microbiomes, (4) senescent cells. Footnote corrected.
  3. Ortega-Molina 2012 female lifespan WRONG in body and footnote. “+9% longer (females, p<0.01)” → “+16% longer (females, p<0.01)” per Figure 2A of the paper. The +12% figure applies to males (correctly stated). Both body text and footnote corrected.
  4. Tyner 2002 lifespan reduction IMPRECISE in body. “~20–25% median reduction” → “23% median reduction (96 wk vs 118 wk; authors’ own framing).” Footnote also updated.
  5. Tyner 2002 strain IMPRECISE in footnote. “(C57BL/6)” → “(C57BL/6×129/Sv mixed background)” per paper Methods.
  6. Baker 2016 BubR1^H/H^ WRONG ATTRIBUTION in body and footnote. Baker 2016 used naturally aged mice only; clearance in progeroid BubR1^H/H^ mice was Baker 2011 (doi:10.1038/nature10232), a separate paper. Body and footnote corrected; note added distinguishing Baker 2011 from Baker 2016.
  7. Baker 2016 tumor claim OVERSTATED. Wiki said “senescent-cell clearance delayed tumor formation” implying reduced incidence. Paper explicitly states: “AP treatment had no impact on the incidence or spectrum of macroscopically detectable tumors at autopsy, although tumor latency was increased.” Corrected to “increased tumor latency but did NOT reduce tumor incidence.”
  8. Jaiswal 2014 CHIP hematologic cancer HR WRONG in body and footnote. Wiki stated “HR 1.9–2.0 for hematologic malignancy” — this is the CV endpoint range (CHD HR 2.0, stroke HR 2.6), not the cancer endpoint. Actual hematologic cancer HR = 11.1 (95% CI 3.9–32.6, fixed-effects meta-analysis, P<0.001). Body and footnote corrected; all endpoint HRs added with exact CIs; CHIP prevalence by age bracket added (9.5% at 70-79, 11.7% at 80-89, 18.4% at 90+).

Pages unverifiable (download failed):

  • Guevara-Aguirre 2011 — green OA status but archive cannot retrieve; no-fulltext-access retained
  • Vasan & Cantley 2022 — green OA status but archive cannot retrieve; no-fulltext-access retained

Downstream pages to check (propagation by main agent):

  • p53 — may carry Tyner 2002 strain “(C57BL/6)” error; correct to “(C57BL/6×129/Sv mixed background)”
  • apoptosis-pathway — pre-verified; Tyner 2002 strain correction may need propagating
  • pten — pre-verified; Ortega-Molina 2012 female lifespan “+9%” may appear there; correct to “+16%”
  • senolytics — may reference Baker 2016 with BubR1^H/H^ attribution or reduced tumor incidence claim; both should be corrected
  • p21 — may reference Baker 2016; same BubR1/incidence correction needed
  • immunosenescence or chip — may carry “HR 1.9-2.0 for hematologic malignancy” from Jaiswal 2014; correct to HR 11.1 (95% CI 3.9-32.6)
  • anemia-of-aging — already corrected (same session): Jaiswal 2014 prevalence figures corrected there; CHIP HR correction not needed (anemia page used different Jaiswal claims)

[2026-05-04] verify | frailty.md

Pages verified: 1

  • phenotypes/frailty.md — corrections applied (8 substantive changes); verified: true (partial scope — Fried 2001 abstract-only; Rockwood 2007 and Clegg 2013 not_oa; Pahor 2014 abstract-only)

Sources checked:

  • Mitnitski 2001 (10.1100/tsw.2001.58) — downloaded PDF (gold OA); verified
  • Howlett 2013 (10.1093/gerona/glt136) — downloaded PDF (bronze OA); verified
  • Justice 2019 (10.1016/j.ebiom.2018.12.052) — local PDF; verified
  • Fried 2001 (10.1093/gerona/56.3.M146) — PubMed abstract only; full-text PDF blocked by publisher paywall despite bronze OA metadata; partially verified
  • Pahor 2014 (10.1001/jama.2014.5616) — PubMed abstract / JAMA landing page; full-text download failed; partially verified
  • Rockwood 2007 (10.1093/gerona/62.7.722) — not_oa; unverifiable; no-fulltext-access retained
  • Clegg 2013 (10.1016/S0140-6736(12)62167-9) — not_oa; unverifiable; no-fulltext-access retained

Corrections (substantive):

  1. Fried 2001 HRs WRONG. Wiki stated “mortality HR ~6.0, incident disability HR ~4.1, hospitalization HR ~1.8”. PubMed abstract reports unadjusted HRs ranging 1.82–4.46 across all outcomes; adjusted HRs 1.29–2.24. No HR ~6.0 appears in the abstract. Corrected to abstract-confirmed range; outcome-specific breakdown flagged no-fulltext-access.
  2. Mitnitski 2001 n WRONG. Wiki said “n=2,305”. Paper reports n=2,913 in the CSHA database (n=1,468 with death-date data for survival analysis). Corrected in body and footnote.
  3. Mitnitski 2001 variable count WRONG. Wiki said “70 variables”. Paper used 92 variables from CSHA. Corrected in body text and footnote.
  4. Mitnitski 2001 submaximal limit claim WRONG attribution. The “submaximal limit ~0.7” was stated in the wiki’s Mitnitski 2001 footnote but is absent from that paper. Removed from footnote with note that it appears in later Rockwood/Mitnitski work.
  5. Justice 2019 6MWT percentage WRONG. Wiki said “+8.4%”. Table 3 of the paper: baseline 447±83 m, follow-up 468±81 m, difference +21.5±28 m, p=0.012 — this is ~+4.8%. Corrected in body text with exact values. Also added: 4-m gait speed +0.12 m/s (p=0.024), chair-stands −2.2 s (p=0.013), SPPB improved (p=0.003), grip and pulmonary function unchanged.
  6. Howlett 2013 mortality prediction claim OVERSTATED. Wiki body text said “predicts mortality independently”. The paper observed FI acceleration in one aged animal immediately prior to death and explicitly states “a large scale study is needed to explore this idea fully.” The paper does not establish mortality predictive validity. Body text and footnote corrected with accurate limitation language.
  7. Howlett 2013 author citation: First author is Whitehead JC (Howlett SE is last/corresponding). Full author list added to footnote. Paper title: “A Clinical Frailty Index in Aging Mice: Comparisons With Frailty Index Data in Humans.” Strain: C57BL/6J confirmed.
  8. Frailty Index variable count in Assessment table: “30–70 variables” → “≥30 variables (original CSHA formulation used 92)”.
  9. IL-6 biomarker attribution: removed ”[^fried2001]” citation from “Strongest inflammatory predictor of IL-6 in CHS” — IL-6 is not mentioned in Fried 2001 abstract; may be a different CHS analysis. Tagged unsourced.
  10. Pahor 2014: HR 0.82 (95% CI 0.69–0.98, p=0.03) confirmed. Added n per arm (818/817) and persistent mobility disability HR 0.72 (95% CI 0.57–0.91, p=0.006). Footnote substantially expanded.

Pages unverifiable (closed-access or download failed):

  • Fried 2001 — full-text PDF behind paywall; abstract verified only; outcome-specific HRs, weight-loss 5% alternate criterion not confirmed
  • Rockwood 2007 — not_oa; FI submaximal limit ~0.7, exponential mortality relationship, ~3%/0.01 increment claim not independently verified
  • Clegg 2013 — not_oa; prevalence, surgical complication risk, dementia conversion HR not independently verified
  • Pahor 2014 — abstract verified; intervention protocol details (center-based vs home-based breakdown) not independently confirmed

Downstream pages to check (propagation by main agent):

[2026-05-04] verify | cardiac-fibrosis.md

Pages verified: 1

  • phenotypes/cardiac-fibrosis.md — 5 corrections; verified: true (partial scope — Travers 2016 download failed)

Sources checked:

  • Anderson 2019 (10.15252/embj.2018100492) — local PDF; verified
  • Lewis-McDougall 2019 (10.1111/acel.12931) — local PDF; verified
  • Frangogiannis 2020 (10.1093/cvr/cvaa324) — downloaded during this pass; verified
  • Travers 2016 (10.1161/CIRCRESAHA.115.306565) — download failed; no-fulltext-access on footnote

Corrections:

  1. SASP absent-list: “IL-6, IL-1β, MMP3” → “IL-6, IL-1β, Cxcl1, Cxcl2” — MMP3 not in Anderson 2019 CM SASP absent list
  2. Senolytic wikilink error: quercetin [[fisetin]] → quercetin (D+Q) — fisetin is not quercetin
  3. Anderson 2019 footnote: full dosing precision added (50 mg/kg/day × 2 cycles; start ~100 wk/~23 mo; analysis ~24 mo; n=5–8/group; Sirius Red ~4%→~2.5%); SASP corrected to Edn3/Tgfb2/Gdf15
  4. Limitations navitoclax entry: full mouse age and dosing protocol added
  5. Lewis-McDougall 2019 footnote: n=35 human donors; >50% senescent in >70 y; classical SASP (MMP-3, PAI-1, IL-6, IL-8, IL-1β, GM-CSF); D+Q and INK-ATTAC in vivo (not navitoclax); age 27.7 ± 2.7 months

Downstream pages to check (propagation by main agent):

[2026-05-04] verify | anemia-of-aging.md

Pages verified: 1

  • phenotypes/anemia-of-aging.md — corrections applied (8 substantive changes); verified: true (partial scope: Nemeth 2004 not_oa, IL-6/hepcidin claims unverified against full PDF)

Sources checked:

  • Guralnik 2004 (10.1182/blood-2004-05-1812) — downloaded PDF; verified (bronze OA)
  • Jaiswal 2014 (10.1056/NEJMoa1408617) — local PDF; verified
  • Genovese 2014 (10.1056/NEJMoa1409405) — downloaded PDF; verified (bronze OA)
  • Sudo 2000 (10.1084/jem.192.9.1273) — local PDF; verified
  • Beerman 2010 (10.1073/pnas.1000834107) — local PDF; verified
  • Nemeth 2004 (10.1172/JCI20945) — not_oa; unverifiable; no-fulltext-access retained

Corrections (substantive):

  1. Jaiswal 2014 CHIP prevalence figures WRONG in body and footnote. Wiki said “~10% at age 65–69, rising to >25–30% by age ≥80.” Paper reports: 5.6% age 60–69, 9.5% age 70–79, 11.7% age 80–89, 18.4% age ≥90. Corrected in body and footnote; “>20% at ≥80” removed.
  2. Genovese 2014 study design mis-stated in footnote: “whole-genome sequencing” → “whole-exome sequencing”; “Iceland cohort” → “Swedish national cohort”; n=2,728 → n=12,380. Body text “Iceland-based” corrected to “Swedish whole-exome sequencing study.”
  3. Genovese 2014 footnote expanded with actual primary results: hematologic cancer HR 12.9 (95% CI 5.8–28.7), death HR 1.4 (95% CI 1.0–1.8); archive status updated to local PDF path.
  4. Guralnik 2004 footnote n corrected: n=3,758 → n=4,199 (paper states 4,199 persons ≥65 in hemoglobin analyses); archive status updated to local PDF path; cause breakdown refined to exact paper values (~34% nutritional, ~33.6% UA, ~32% ACI/renal).
  5. Jaiswal 2014 footnote expanded with exact CIs: CHD HR 2.05 (95% CI 1.2–3.4), stroke HR 2.6 (95% CI 1.4–4.8), all-cause HR 1.4 (95% CI 1.1–1.8).
  6. Sudo 2000 footnote age range corrected: “young (8–12 wk)” → “2-month-old (young)”; “aged (18–22 mo)” → “18-month-old (aged)”; added clarification that 17.4-fold refers to total CD34⁻KSL, not functional HSC subset (which expands only ~2.2-fold).
  7. Beerman 2010 footnote age range corrected: “young (8–12 wk)” → “young adult (4 mo)”; “aged (20–24 mo)” → “old (22–24 mo)”; confirmed exactly 2 subsets (not 3).
  8. Adverse outcomes mortality claim: “HR ~1.5 all-cause [^guralnik2004]” removed — Guralnik 2004 is a prevalence study that does not report a mortality HR. Replaced with description noting the association and tagging unsourced for the specific HR.
  9. Body text HSC expansion claim clarified: the “~17-fold” figure refers to total CD34⁻KSL pool, not the functional HSC subset (which is only 2.2-fold); majority of expansion is defective HSCs and progenitors.

Pages unverifiable (closed-access):

  • Nemeth 2004 (10.1172/JCI20945) — not_oa; IL-6 → hepcidin mechanism claims (JAK1/STAT3 pathway, ferroportin internalization) not independently verified from full text

[2026-05-04] verify | alzheimers-disease.md

Pages verified: 1

  • phenotypes/alzheimers-disease.md — corrections applied (6 substantive changes); verified: true (partial scope: Hardy 1992, Hardy 2002, Corder 1993 closed-access; Jonsson 2013 PDF unavailable)

Sources checked:

  • Hara 2006 (10.1038/nature04724) — local PDF; verified (Atg5 paper, pages 885-889)
  • Komatsu 2006 (10.1038/nature04723) — local PDF; verified (Atg7 paper, pages 880-884)
  • Guerreiro 2013 (10.1056/NEJMoa1211851) — local PDF; verified
  • van Dyck 2023 (10.1056/NEJMoa2212948) — downloaded PDF; verified
  • Sims 2023 (10.1001/jama.2023.13239) — downloaded PDF; verified
  • Strittmatter 1993 (10.1073/pnas.90.5.1977) — downloaded PDF; verified
  • Jonsson 2013 (10.1056/NEJMoa1211103) — PDF download failed (green OA but mirrors inaccessible); OR verified via PubMed abstract; tagged no-fulltext-access on footnote
  • Hardy & Higgins 1992 (10.1126/science.1566067) — not_oa; unverifiable
  • Hardy & Selkoe 2002 (10.1126/science.1072994) — not_oa; unverifiable
  • Corder 1993 (10.1126/science.8346443) — not_oa; unverifiable

Corrections (substantive):

  1. Hara 2006 / Komatsu 2006 gene assignments REVERSED in body text and footnotes. Body text said “conditional Atg7 KO” for [^hara2006] and “conditional Atg5 KO” for [^komatsu2006] — corrected to Atg5 (Hara) and Atg7 (Komatsu). Footnote DOIs swapped: [^hara2006] had doi:10.1038/nature04723 (Komatsu’s DOI) → corrected to doi:10.1038/nature04724; [^komatsu2006] had doi:10.1038/nature04724 → corrected to doi:10.1038/nature04723. Study page wikilinks also corrected accordingly.
  2. Donanemab ARIA rates: wiki said “ARIA rates similar to lecanemab” — INCORRECT. Sims 2023 Table 3: donanemab ARIA-E 24.0% (205/860) and ARIA-H 31.4% (268/860), substantially higher than lecanemab’s 12.6%/17.3%. Body text and footnote corrected.
  3. Guerreiro 2013 footnote: “exome sequencing ~2,000 AD cases + controls” → corrected to “discovery n=1,092 cases + 1,107 controls; full combined series n=1,994 cases + 4,062 controls OR=5.05 (95% CI 2.77–9.16)”; discovery-set OR=4.5 (95% CI 1.7–11.9) preserved as Table 2 value.
  4. Jonsson 2013 footnote: archive status updated from “downloading (green OA)” → “PDF unavailable from accessible mirrors; OR verified via PubMed abstract”; combined OR 2.90 (95% CI 2.16–3.91) added; no-fulltext-access tagged.
  5. van Dyck 2023 footnote: expanded with per-arm n (898/897 randomized; mITT 859/875), absolute CDR-SB values (1.21 vs 1.66), and confirmed ARIA denominator (n=898 safety population); archive status updated from “bronze OA pending” to local PDF path.
  6. Sims 2023 footnote: expanded with per-arm n (860/876), exact iADRS CIs (35.1% 19.90–50.23%; 22.3% 11.38–33.15%), CDR-SB secondary results (36.0%/28.9%), correct ARIA figures (ARIA-E 24.0%, ARIA-H 31.4%), 3 treatment-related deaths; archive status updated to local PDF path.

Pages unverifiable (closed-access):

  • Hardy & Higgins 1992 — not_oa; amyloid cascade hypothesis framing claims not independently verified from full text
  • Hardy & Selkoe 2002 — not_oa; soluble oligomer toxicity claims not independently verified
  • Corder 1993 — not_oa; APOE ε4 dose-response risk ratios (~3–4× / ~12×) not independently verified from full text

Downstream pages to check (propagation by main agent):

[2026-05-04] verify | heart-failure.md

Pages verified: 1

  • phenotypes/heart-failure.md — corrections applied (8 substantive changes); verified: true (partial scope: Heidenreich 2022 full-text unavailable)

Sources checked:

  • Anderson 2019 (10.15252/embj.2018100492) — local PDF; verified
  • Bergmann 2015 (10.1016/j.cell.2015.05.026) — local PDF; verified
  • Lewis-McDougall 2019 (10.1111/acel.12931) — local PDF; verified
  • Wang 2013 (10.1101/gad.215855.113) — local PDF; verified
  • McMurray 2014 PARADIGM-HF (10.1056/NEJMoa1409077) — downloaded PDF; verified
  • Anker 2021 EMPEROR-Preserved (10.1056/NEJMoa2107038) — downloaded PDF; verified
  • Solomon 2022 DELIVER (10.1056/NEJMoa2206286) — downloaded PDF; verified
  • Heidenreich 2022 (10.1161/CIR.0000000000001063) — download failed (AHA journal blocked); no-fulltext-access; guideline epidemiology/classification claims not independently verified from full-text

Corrections (substantive):

  1. Navitoclax age: “24-month” → “23-month (100 weeks at start of treatment)” per Anderson 2019 Fig 8A legend and Methods
  2. D+Q EdU+ attribution clarified: EdU+ ~0.25% data is from AP/INK-ATTAC genetic clearance arm (Fig 6h), not D+Q; D+Q has Ki67+ ~0.25% data only (Fig 6f); vehicle comparators corrected (~0.03% Ki67+; 0.07 ± 0.00% old vehicle EdU+)
  3. CPC SASP list expanded: “PAI-1, IL-8, IL-6, GM-CSF” → “PAI-1, IL-8, IL-1β, IGFBP-3, CCL-2, IL-6, GM-CSF” (7 proteins confirmed by Luminex in Lewis-McDougall Fig 4b)
  4. CPC senescence description corrected: p16INK4A+ and SA-β-gal+ are separate findings (not combined) per Lewis-McDougall Fig 1a,b; linear correlation R²=0.722 added; ~60% SA-β-gal+ in old vs ~20% middle-aged added
  5. Anderson 2019 footnote: SASP species corrected to “Edn3, Tgfb2, Gdf15” with full not-expressed list (Il-1α, Il-1β, Il-6, Cxcl1, Cxcl2); n per group corrected to n=5–8 (navitoclax)/n=6 (INK-ATTAC); mice described as mixed-sex
  6. Lewis-McDougall footnote: in vivo mouse age 27.7 ± 2.7 months added; EdU+ attribution disambiguated; SASP expanded to 7 proteins
  7. EMPEROR-Preserved ~49% T2D confirmed from Table 1 (1,466/2,997 = 48.9%); gap tag removed
  8. All three trial footnotes updated with full verified numerics and PDF availability; Heidenreich footnote updated with no-fulltext-access

Downstream pages to check (propagation by main agent):

  • cardiomyocytes — already verified; navitoclax age correction may be needed if “24-month” appears there
  • senolytics — may cite Lewis-McDougall SASP list or D+Q/navitoclax ages

[2026-05-04] verify | neurodegeneration.md

Pages verified: 1

  • phenotypes/neurodegeneration.md — corrections: 5

Corrections made:

  1. Hara 2006 Cre driver: “CaMKII-Cre” → “nestin-Cre” (Atg5^flox/flox × nestin-Cre) — both in body text and footnote; CaMKII-Cre was wrong attribution
  2. Hara 2006 footnote: removed erroneous cross-reference “also verified on atg7 page” (Hara 2006 is the Atg5 paper, not Atg7); added death-within-weeks survival detail
  3. Komatsu 2006 footnote: added n (n=26 mutants, 41 controls from KM curve), added “death within 28 weeks” and “proteasome function unaffected” per paper
  4. Bouzid 2023: n corrected from wrong “>47,000” to “5,730 (1,362 AD; 4,368 controls)”; “three independent cohorts” claim removed (not confirmed in abstract — paper says “meta-analysis” without specifying cohort count in abstract); Mendelian randomization finding and microglia brain-fraction result added
  5. Wong & Cuervo 2010 footnote: removed “not yet cross-checked” — all three NDD-specific claims (PD CMA block, AD autophagic vacuoles as Aβ source, HD CMA block) verified against local PDF; DOI path corrected (stale local mount mount → actual path noted)

Pages unverifiable (closed-access):

  • 10.1038/nature10317 (Hartl 2011) — not_oa; consensus-level claims; kept
  • 10.1038/nature05292 (Lin & Beal 2006) — not_oa; kept with no-fulltext-access on footnote
  1. van Dyck 2023 ARIA-E rate: “~21%” → 12.6% (per Table 3, safety population n=898); ARIA-H: “~35%” → 17.3%; combined ARIA-E or ARIA-H 21.5% added; all CDR-SB primary endpoint values confirmed (1.21 vs 1.66, diff −0.45, P<0.001)

Pages unverifiable (closed-access or download failed):

  • 10.1038/nature10317 (Hartl 2011) — not_oa
  • 10.1038/nature05292 (Lin & Beal 2006) — not_oa
  • 10.1111/jnc.13607 (DiSabato 2016) — bronze OA, download failed (no PMC URL); tagged no-fulltext-access

Downstream pages to check (main agent):

  • bouzid-2023-chip-alzheimers — study page not yet seeded; n=5,730 must be used when seeded
  • lc3 — cites Hara 2006; confirm Cre driver is correct there (CaMKII-Cre vs nestin-Cre)

[2026-05-04] verify | parkinsons-disease.md

Pages verified: 1

  • phenotypes/parkinsons-disease.md — corrections applied (4 substantive changes); verified: true (partial scope — 4 of 8 cited sources unverifiable; see verified-scope)

Sources checked:

  • Sidransky 2009 (10.1056/NEJMoa0901281) — downloaded PDF; verified
  • Zimprich 2004 (10.1016/j.neuron.2004.11.005) — downloaded PDF; verified
  • Postuma 2015 (10.1002/mds.26424) — abstract only (PDF download failed, bronze OA); parkinsonism definition verified against abstract
  • Spillantini 1997 (10.1038/42166) — download failed twice (bronze OA); no-fulltext-access
  • Polymeropoulos 1997 (10.1126/science.276.5321.2045) — not_oa; no-fulltext-access
  • Kitada 1998 (10.1038/33416) — not_oa; no-fulltext-access
  • Valente 2004 (10.1126/science.1096284) — download failed twice (green OA figshare URL returned HTTP 202; Science paywalled); no-fulltext-access
  • Bonifati 2003 (10.1126/science.1077209) — not_oa; no-fulltext-access

Corrections (substantive):

  1. Parkinsonism definition (intro + diagnostic criteria section): “bradykinesia plus at least one of: resting tremor, rigidity, or postural instability” → “bradykinesia plus rest tremor and/or rigidity” per Postuma 2015 abstract. Postural instability is NOT in the MDS 2015 core parkinsonism definition; note added to both intro and criteria section.
  2. GBA OR (body text): “~5-fold increased risk” → “OR 5.43 (Mantel–Haenszel combined across 16 centers; remained 5.43 or higher in all sensitivity analyses)” per Sidransky 2009 paper. OR = 5.43 is exact; the footnote already had this but the body text understated it.
  3. Zimprich 2004 / G2019S misattribution: Wiki claimed Zimprich 2004 identified G2019S. The Zimprich 2004 paper identified Y1699C, R1441C, I1122V, I2020T, 3342A>G, and one splice site in 34 families — G2019S is absent. G2019S was identified by Paisán-Ruíz 2004 (PMID 15541308), published simultaneously. Table entry and footnote corrected; unsourced tag added for G2019S kinase-activating function (needs West 2005 or equivalent citation).
  4. Zimprich 2004 footnote: corrected to accurately list the 6 mutations identified (no G2019S); clarified that 46 families were sequenced for mapping but mutations found in 34; LRRK2 domain structure (MAPKKK kinase, LRR, ROC, COR, WD40) confirmed against paper.

Unverifiable claims (source not accessible):

  • Spillantini 1997: α-synuclein in Lewy bodies — widely accepted consensus claim; unverifiable from local PDF but claim is not in doubt
  • Polymeropoulos 1997: SNCA A53T in Italian/Greek kindreds — unverifiable from local PDF
  • Kitada 1998: PRKN mutations in AR-JP families — unverifiable from local PDF
  • Valente 2004: PINK1 mutations in PARK6 — unverifiable from local PDF
  • Bonifati 2003: DJ-1 mutations — unverifiable from local PDF
  • Postuma 2015 criterion counts (≥2 supportive for established; ≤1 red flag for probable) — not verifiable from abstract alone; tagged no-fulltext-access
  • Prevalence (~1–2% age 65+; ~4% age 80+) — no primary source cited; remains in frontmatter with unsourced implicit
  • ~70–80% SNc neuron loss threshold — explicitly tagged unsourced; primary source still needed

Downstream pages to check (propagation by main agent):

  • pink1 — cites Valente 2004 for PARK6; framing matches parkinsons-disease.md; no new correction from this verification pass
  • parkin — cites Kitada 1998 for AR-JP; framing matches parkinsons-disease.md; no new correction
  • zimprich-2004-lrrk2-pd — study page should be seeded/corrected to note G2019S was NOT in Zimprich 2004; Paisán-Ruíz 2004 (PMID 15541308) needs a study page and citation on this wiki
  • sidransky-2009-gba-pd — study page should reflect verified OR = 5.43 (exact), n breakdown (780 AJ PD, 4911 non-AJ PD, 387 AJ controls, 4511 non-AJ controls)

[2026-05-04] ingest | round-8c-composite-cancer

cancer

  • added: phenotypes/cancer.md
  • entity type: phenotype (overview/category page — unified aging-cancer paradox framework spanning all tissue types)
  • canonical IDs: ICD-10 null (multi-code overview; C00–D49), ICD-11 null (2A00–2F9Z); no single code applies
  • DOIs cited (10 footnotes):
    • 10.1016/j.cell.2011.02.013 (Hanahan & Weinberg 2011, Cell — Hallmarks of Cancer: The Next Generation) — confirmed in archive, pending download
    • 10.1158/2159-8290.CD-21-1059 (Hanahan 2022, Cancer Discov — New Dimensions) — confirmed in archive, pending download
    • 10.1038/415045a (Tyner 2002, Nature — p53 m-allele trade-off) — archive: local PDF available; pre-verified on p53 and apoptosis-pathway
    • 10.1101/gad.1378506 (Mendrysa 2006, Genes Dev — MDM2 hypomorph aging-normal CORRECTION) — archive: local PDF available; pre-verified on mdm2
    • 10.1016/j.cmet.2012.02.001 (Ortega-Molina 2012, Cell Metab — Pten^tg longevity) — archive: local PDF available; pre-verified on pten
    • 10.1016/j.cell.2012.02.030 (Garcia-Cao 2012, Cell — Super-PTEN cancer-resistant metabolism) — archive: local PDF available; pre-verified on pten
    • 10.1126/scitranslmed.3001845 (Guevara-Aguirre 2011, Sci Transl Med — Laron syndrome zero cancer deaths) — archive: confirmed, download failed no-fulltext-access; pre-verified on insulin-igf1
    • 10.1038/nature16932 (Baker 2016, Nature — INK-ATTAC senolysis delays tumor formation) — archive: local PDF available; pre-verified on p21 and senolytics
    • 10.1056/NEJMoa1408617 (Jaiswal 2014, NEJM — CHIP aging outcomes) — archive: local PDF available; also cited on anemia-of-aging (same session)
    • 10.1056/nejmoa1513257 (Roberts 2016, NEJM — venetoclax CLL) — archive: local PDF available; pre-verified on bcl-2-family-signaling
    • 10.1038/s41571-022-00633-1 (Vasan & Cantley 2022, Nat Rev Clin Oncol — PI3K/AKT in cancer) — archive: confirmed, download failed no-fulltext-access; pre-verified on pi3k-akt-pathway
  • implicit stubs created (new wikilinks to non-existent pages):
    • [[various]] (referenced as affected-tissues placeholder — not a real page; verifier should replace with tissue-specific links if this page is expanded)
    • [[immunosenescence]] — already exists (verified-partial); flagged as inbound
    • [[studies/hanahan-weinberg-2011-hallmarks-cancer]], [[studies/hanahan-2022-hallmarks-cancer-new-dimensions]], [[studies/mendrysa-2006-mdm2-hypomorph]], [[studies/ortega-molina-2012-pten-transgenic-longevity]], [[studies/garcia-cao-2012-super-pten-cancer-resistance]], [[studies/guevara-aguirre-2011-laron-syndrome-cancer]], [[studies/jaiswal-2014-chip-aging-outcomes]] (study pages not yet created — Tyner 2002, Baker 2016, Roberts 2016 already have study pages)
  • cross-references to existing pages: [[p53]], [[mdm2]], [[pten]], [[pi3k-akt-pathway]], [[p21]], [[cellular-senescence]], [[apoptosis]], [[apoptosis-pathway]], [[bcl-2-family-signaling]], [[bcl-2]], [[insulin-igf1]], [[telomere-attrition]], [[immunosenescence]], [[interventions/pharmacological/senolytics]], [[interventions/pharmacological/senomorphics]], [[atm]], [[chronic-inflammation]], [[growth-hormone]], [[foxo4]], [[heterocephalus-glaber]]
  • gaps surfaced:
    • #gap/no-fulltext-access — Guevara-Aguirre 2011 (failed download); Vasan&Cantley 2022 (failed download); Hanahan&Weinberg 2011 + Hanahan 2022 (pending download)
    • #gap/needs-human-replication — Tyner 2002 p53 trade-off (mouse only); PTEN GOF longevity + cancer resistance (mouse only); senolytic cancer prevention (mouse only)
    • #gap/needs-replication — Laron syndrome cancer protection (single Ecuador cohort, n~100); CHIP-to-cancer progression rates (cohort estimates vary); Garcia-Cao Super-PTEN metabolic protection (no lifespan data)
    • #gap/no-mechanism — why aged SASP accumulates despite immune clearance decline (quantitative contribution unresolved); tumor microenvironment vs intrinsic mutation rate dominance unclear
    • #gap/contradictory-evidence — somatic mutation accumulation vs permissive microenvironment as primary driver of age-incidence exponential curve; senolytic cancer promotion risk vs benefit
    • #gap/long-term-unknown — MDM2 inhibitor drugs (nutlin-class) for aging trade-off in chronic dosing; senolytic therapeutic window in oncology
    • #gap/unsourced — mutation accumulation rate per cell-division from somatic clock studies not yet formally cited
  • schema notes: icd-10: null and icd-11: null follow neurodegeneration and cardiovascular-aging precedents for multi-disease overview pages. affected-tissues: ["[[various]]"] is a placeholder not used on any other page — verifier may want to enumerate major affected tissue types or remove the affected-tissues field entirely for an overview page. Escalating this as a minor schema gap: the phenotype schema does not have guidance for overview pages that span all tissues. Used [[various]] as an explicit placeholder to avoid frontmatter invalidation.
  • verification priority: Tyner 2002 (local PDF, pre-verified on p53/apoptosis-pathway — cross-check m-allele description), Mendrysa 2006 (local PDF, pre-verified on mdm2 — CRITICAL CORRECTION already applied), Ortega-Molina 2012 + Garcia-Cao 2012 (local PDFs, pre-verified on pten — cross-check PTEN quantitative details), Baker 2016 (local PDF, pre-verified on p21/senolytics). Hanahan&Weinberg 2011 cancer hallmarks list should be verified once PDF downloads complete.

anemia-of-aging

  • added: phenotypes/anemia-of-aging.md
  • entity type: phenotype
  • canonical IDs: ICD-10 D64.9, ICD-11 3A00.Z
  • DOIs cited (6 footnotes):
    • 10.1182/blood-2004-05-1812 (Guralnik 2004, Blood — NHANES III anemia epidemiology, 1,429 citations, archive: bronze OA, pending)
    • 10.1172/JCI20945 (Nemeth 2004, JCI — IL-6→hepcidin axis, 2,221 citations, archive: not_oa, no-fulltext-access)
    • 10.1056/NEJMoa1408617 (Jaiswal 2014, NEJM — CHIP epidemiology and outcomes, 4,510 citations, archive: local PDF available)
    • 10.1056/NEJMoa1409405 (Genovese 2014, NEJM — CHIP replication/blood cancer risk, 3,344 citations, archive: bronze OA, pending)
    • 10.1084/jem.192.9.1273 (Sudo 2000, JEM — HSC aging characteristics, archive: local PDF available; pre-verified on hematopoietic-stem-cells.md)
    • 10.1073/pnas.1000834107 (Beerman 2010, PNAS — myeloid-biased HSC expansion, archive: local PDF available; pre-verified on hematopoietic-stem-cells.md)
  • implicit stubs created (new wikilinks to non-existent pages):
    • [[peripheral-blood]] (tissue page)
    • [[metformin]] (compound page — referenced for B12 depletion; per task brief this page is verified-partial on DPP B12 finding)
    • [[studies/guralnik-2004-anemia-aging-nhanes]], [[studies/nemeth-2004-il6-hepcidin-anemia-inflammation]], [[studies/jaiswal-2014-chip-aging-outcomes]], [[studies/genovese-2014-chip-blood-cancer]], [[studies/sudo-2000-hsc-aging-characteristics]], [[studies/beerman-2010-hsc-myeloid-bias-aging]] (study pages)
  • cross-references to existing pages: [[hematopoietic-stem-cells]] (verified-partial), [[stem-cell-exhaustion]] (stub), [[chronic-inflammation]] (stub), [[genomic-instability]] (stub), [[immunosenescence]] (verified-partial), [[sarcopenia]] (verified-partial), [[bone-marrow]] (stub, created by frailty.md), [[hallmarks-of-aging]]
  • gaps surfaced:
    • #gap/no-fulltext-access — Nemeth 2004 JCI (not_oa)
    • #gap/no-mechanism — UAA ~30–35% of geriatric anemia; myeloid bias → erythroid output link not directly demonstrated; EPO hyporesponsiveness mechanism in UAA
    • #gap/needs-human-replication — senolytic potential for anemia of aging (preclinical only)
    • #gap/contradictory-evidence — CHIP → anemia causality direction
    • #gap/needs-replication — EPO hyporesponsiveness in UAA (small studies)
    • #gap/unsourced — metformin-B12 claim (deferred to metformin page); Hb threshold debate for frail elderly
  • schema note: affected-tissues includes [[hematopoietic-stem-cells]] — this is a cell-type page, not a tissue, but is the most direct affected entity. Follows precedent from CLAUDE.md example showing cell-type pages in affected-tissues field. No schema divergence.
  • verification priority: Jaiswal 2014, Sudo 2000, Beerman 2010 all have local PDFs — verify the 17× HSC expansion figure (Sudo), CHIP prevalence and HR figures (Jaiswal), and Slamf1-hi expansion claim (Beerman). Guralnik 2004 (the epidemiology backbone — ~33% each etiology) is highest-impact for the page but download pending.

[2026-05-04] ingest | round-8c-composite-frailty

frailty

  • added: phenotypes/frailty.md
  • entity type: phenotype (composite multi-system geriatric syndrome)
  • canonical IDs: ICD-10 R54, ICD-11 MG2A
  • DOIs cited (6 footnotes):
    • 10.1093/gerona/56.3.M146 (Fried 2001, J Gerontol — Fried Frailty Phenotype, 23,384 citations, archive: pending bronze OA)
    • 10.1100/tsw.2001.58 (Mitnitski 2001 — Frailty Index, archive: pending gold OA)
    • 10.1093/gerona/62.7.722 (Rockwood 2007 — FI properties, archive: not_oa no-fulltext-access)
    • 10.1016/S0140-6736(12)62167-9 (Clegg 2013, Lancet — frailty review, archive: not_oa no-fulltext-access)
    • 10.1093/gerona/glt136 (Howlett 2013 — mouse Frailty Index, archive: pending bronze OA)
    • 10.1016/j.ebiom.2018.12.052 (Justice 2019 — D+Q in IPF, archive: local PDF available; pre-verified on senolytics.md)
    • 10.1001/jama.2014.5616 (Pahor 2014 LIFE trial, JAMA — exercise RCT, archive: pending green OA)
  • DOI correction (BUG-2): task brief cited 10.1016/j.mad.2013.12.003 for “Howlett 2014 frailty index in mice” — DOI lookup confirms this resolves to “Nutrition, diet and immunosenescence” (Mechanisms of Ageing and Development, 77 citations). Correct DOI confirmed via Crossref + archive: 10.1093/gerona/glt136 (Howlett 2013, J Gerontol, 486 citations). Corrected on page with explanatory note in footnote.
  • implicit stubs created (new wikilinks to non-existent pages):
    • [[bone-marrow]] (tissue page, referenced as affected tissue)
    • [[studies/fried-2001-frailty-phenotype]], [[studies/mitnitski-2001-frailty-index]], [[studies/rockwood-2007-frailty-deficits]], [[studies/clegg-2013-frailty-lancet]], [[studies/howlett-2013-mouse-frailty-index]], [[studies/pahor-2014-life-trial]] (study pages)
    • [[neural-stem-cells]] (referenced in cognitive frailty subtype section)
  • cross-references to existing pages: [[sarcopenia]] (verified-partial), [[immunosenescence]] (verified-partial), [[cellular-senescence]] (stub), [[chronic-inflammation]] (stub), [[stem-cell-exhaustion]] (stub), [[mitochondrial-dysfunction]] (stub), [[deregulated-nutrient-sensing]] (stub), [[hematopoietic-stem-cells]] (verified-partial), [[interventions/pharmacological/senolytics]] (verified-partial), [[interventions/lifestyle/caloric-restriction]] (verified-partial), [[neurodegeneration]] (drafted), [[alzheimers-disease]] (drafted), [[mtor]] (verified-partial)
  • gaps surfaced:
    • #gap/needs-human-replication — direct senolytic reversal of frailty-defining endpoints; mouse FI → human frailty concordance
    • #gap/contradictory-evidence — chronic inflammation causality direction (upstream vs downstream); vitamin D supplementation in frailty
    • #gap/no-mechanism — DHEA-S inverse frailty association causality
    • #gap/no-fulltext-access — Rockwood 2007 (not_oa); Clegg 2013 Lancet (not_oa)
    • #gap/needs-replication — HR estimates for adverse outcomes (vary widely across studies); biomarker panel validation; frailty reversibility in ≥75 age group; cognitive frailty subtype mechanistic evidence
    • #gap/long-term-unknown — exercise reversibility in severe frailty; TAME trial (metformin) results pending ~2027
  • schema notes: ICD-10 R54 (“Senility”) is the current code used for frailty; ICD-11 MG2A (“Frailty”) is the more specific code. Both included per CLAUDE.md phenotype schema. No new schema fields required. [[bone-marrow]] added to affected-tissues following the sarcopenia prototype precedent (tissue wikilinks in frontmatter list).
  • verification priority: Justice 2019 (local PDF) is pre-verified on senolytics.md — can use for cross-check on the 6MWT and dosing claims. Fried 2001, Mitnitski 2001, and Pahor 2014 are download-pending and should be prioritized for quantitative claim verification (HR estimates, prevalence figures, primary outcome stats).

[2026-05-04] ingest | round-8b-cardiovascular

cardiovascular-aging

  • added: phenotypes/cardiovascular-aging.md
  • entity type: phenotype (overview/category page — system-level cardiovascular aging spanning vascular stiffening, cardiac senescence, HFpEF predisposition, CPC exhaustion, atherosclerosis, and conduction system changes)
  • canonical-DB IDs: ICD-10 null, ICD-11 null (multi-phenotype overview; no single ICD code applies)
  • DOIs cited (8 footnotes):
    • 10.1161/01.CIR.0000048893.62841.F7 (Lakatta & Levy 2003, Circulation) — confirmed in archive, closed-access, not locally available
    • 10.1161/CIRCULATIONAHA.109.886655 (Mitchell 2010, Framingham arterial stiffness) — confirmed in archive, closed-access, not locally available
    • 10.1161/CIRCRESAHA.111.246876 (North & Sinclair 2012) — confirmed in archive, bronze OA, download pending
    • 10.15252/embj.2018100492 (Anderson 2019, CM senescence) — local PDF available; pre-verified on cardiomyocytes
    • 10.1016/j.cell.2015.05.026 (Bergmann 2015, CM turnover 14C) — local PDF available; pre-verified on cardiomyocytes
    • 10.1126/science.aaf6659 (Childs 2016, senolytic atherosclerosis) — confirmed in archive, closed-access, not locally available no-fulltext-access
    • 10.1161/CIRCRESAHA.118.312563 (Donato 2018, vascular aging) — confirmed in archive, bronze OA, download pending
    • 10.1111/acel.12931 (Lewis-McDougall 2019, CPC senescence) — local PDF available; pre-verified on cardiomyocytes
  • implicit stubs created (new wikilinks to non-existent pages):
    • [[myocardium]], [[arterial-wall]], [[endothelium]], [[cardiac-fibroblasts]] (tissue/cell-type pages)
    • [[heart-failure]] (R8b parallel — may be drafted this round)
    • [[studies/anderson-2019-cm-senescence-sasp]], [[studies/bergmann-2015-cm-turnover]], [[studies/lewis-mcdougall-2019-cpc-senescence]] (study pages)
  • gaps surfaced:
    • #gap/needs-human-replication — senolytic cardiac benefits; rapamycin cardiac benefits; non-canonical CM SASP paracrine significance; CPC senescent fraction as therapeutic target
    • #gap/no-fulltext-access — Childs 2016 (Science); Lakatta 2003 (Circulation); Mitchell 2010 (Circulation)
    • #gap/unsourced — sinus node cell loss ~75% figure; AF prevalence >10% at age 80
    • #gap/contradictory-evidence — GDF11 rejuvenation; CPC identity in adult human heart; causality direction aging vs risk factors
    • #gap/dose-response-unclear — optimal aerobic exercise dose/type for vascular stiffness reversal
    • #gap/no-mechanism — ATTR-wt amyloidosis aging trigger; senescent cell load quantification for clinical use
  • schema note: overview/category phenotype with icd-10: null follows neurodegeneration precedent (R8a). No new schema decisions required.
  • verification priority: Anderson 2019 + Bergmann 2015 + Lewis-McDougall 2019 locally available and pre-verified on cardiomyocytes — suggest verifier use those first; PWV ~50% rise claim from Mitchell 2010 which is closed-access.

[2026-05-04] ingest | round-8a-disease-entities

neurodegeneration

  • added: phenotypes/neurodegeneration.md
  • entity type: phenotype (overview/category page covering AD, PD, ALS, HD, FTD, prion diseases, MSA, PSP, CBD, DLB as a class)
  • canonical-DB IDs: none applicable (multi-disease overview; ICD-10/ICD-11 null; covers G10/G12/G20/G30/G31/G23/A81 codes listed in body table)
  • DOIs cited (8 footnotes):
    • 10.1038/nature10317 (Hartl 2011 proteostasis review) — confirmed in archive, not_oa
    • 10.1038/nature04724 (Hara 2006 Atg5 KO) — confirmed in archive, local PDF available, pre-verified on atg7/lc3 pages
    • 10.1038/nature04723 (Komatsu 2006 Atg7 KO) — confirmed in archive, local PDF available, pre-verified on atg7 page
    • 10.1038/nn.2575 (Wong & Cuervo 2010 autophagy+neurodegeneration review) — confirmed in archive, local PDF available
    • 10.1038/nature05292 (Lin & Beal 2006 mitochondrial dysfunction in NDD) — confirmed in archive, not_oa (#gap/no-fulltext-access)
    • 10.1111/jnc.13607 (DiSabato 2016 neuroinflammation review) — confirmed in archive, download pending (bronze OA)
    • 10.1038/s41591-023-02397-2 (Bouzid 2023 CHIP-AD) — confirmed in archive, local PDF available
    • 10.1056/nejmoa2212948 (lecanemab CLARITY-AD, van Dyck 2023) — confirmed in archive, download pending (bronze OA)
  • DOI correction: task brief cited 10.1038/nm.2245 for “Wong & Cuervo 2010” — this resolves to a nNOS/PSD-95 cerebral ischemia paper (title mismatch). Correct DOI is 10.1038/nn.2575 (confirmed via PubMed PMID 20581817 + DOI lookup title match).
  • implicit stubs created (new wikilinks to non-existent pages):
    • [[tau]], [[alpha-synuclein]], [[sod1]], [[tdp-43]], [[huntingtin]], [[trem2]], [[pink1]], [[ubiquitin-proteasome-system]], [[neural-stem-cells]], [[unfolded-protein-response]]
    • [[brain]], [[spinal-cord]] (tissues)
    • [[studies/hartl-2011-proteostasis-review]], [[studies/hara-2006-atg5-neural-autophagy]], [[studies/komatsu-2006-atg7-neural-autophagy]], [[studies/wong-cuervo-2010-autophagy-neurodegeneration]], [[studies/bouzid-2023-chip-alzheimers]] (study pages)
  • gaps surfaced:
    • #gap/no-fulltext-access — Lin & Beal 2006 (not_oa)
    • #gap/no-mechanism — selective neuronal vulnerability; CHIP-AD protective mechanism
    • #gap/needs-replication — complement synapse elimination; CMA blockade claims (from review, not primary)
    • #gap/needs-human-replication — chaperone capacity aging decline; autophagy therapy in human NDD
    • #gap/contradictory-evidence — causal direction neuroinflammation vs neurodegeneration; somatic mosaicism
    • #gap/long-term-unknown — lecanemab clinical benefit durability
    • #gap/unsourced — proteasome activity decline in aged brain (broad consensus, no specific primary cited); MSA/PSP/CBD mechanistic claims
  • schema note: task brief DOI 10.1038/nm.2245 confirmed incorrect for Wong & Cuervo 2010 (see DOI correction above); no schema ambiguity encountered for the overview/category page type — used standard phenotype schema with icd-10: null + explanatory comment as precedent.

type-2-diabetes

  • added: phenotypes/type-2-diabetes.md
  • entity type: phenotype
  • canonical IDs: ICD-10 E11, ICD-11 5A11
  • DOIs cited (8 footnotes):
    • 10.2337/dc24-S002 (ADA 2024 Standards of Care — local PDF available)
    • 10.1038/36116 (Withers 1998 Irs2-/- T2D — not_oa, no-fulltext-access)
    • 10.1038/nature02866 (Um 2004 S6K1-IRS-1 insulin sensitivity — local PDF available, pre-confirmed on s6k1.md)
    • 10.1126/science.1142358 (Saxena 2007 TCF7L2 GWAS — not_oa, no-fulltext-access)
    • 10.1016/j.cmet.2019.05.006 (Aguayo-Mazzucato 2019 beta-cell senescence — archive pending)
    • 10.1056/NEJMoa1504720 (Zinman 2015 EMPA-REG OUTCOME — archive pending)
    • 10.1056/NEJMoa1607141 (Marso 2016 SUSTAIN-6 semaglutide CV — archive pending)
    • 10.1056/NEJMoa2032183 (Wilding 2021 STEP-1 semaglutide weight — not_oa)
  • task-brief citation correction: brief attributed EMPA-REG to “Marso 2016 (10.1056/NEJMoa1607141)” — DOI lookup confirms 10.1056/NEJMoa1607141 is SUSTAIN-6 (semaglutide), not EMPA-REG (empagliflozin). Correct EMPA-REG citation is Zinman 2015 (10.1056/NEJMoa1504720). Both cited correctly on the page.
  • implicit stubs created:
    • [[adipose-tissue]], [[pancreas]] (tissue pages)
    • [[glut4]] (glucose transporter, mentioned in IRS-1→GLUT4 mechanism)
    • [[foxo1]] (FOXO1 hepatic suppression, referenced via pi3k-akt-pathway)
    • [[alzheimers-disease]] (T2D-AD bidirectional risk — now drafted in R8a)
  • gaps surfaced:
    • #gap/needs-human-replication — beta-cell senescence (Aguayo-Mazzucato 2019 mouse only); brain-IIS paradox; SGLT2i aging-specific lifespan
    • #gap/contradictory-evidence — mitochondrial defect causality (primary vs secondary)
    • #gap/long-term-unknown — TAME trial results pending ~2027; S6K1 inhibitor clinical gap
    • #gap/no-mechanism — T2DM-aging causality direction (aging causes T2D vs T2D accelerates aging)
    • #gap/no-fulltext-access — Withers 1998, Saxena 2007, Wilding 2021 (closed-access)

[2026-05-04] verify | growth-hormone

Pages verified: 1 (partial scope — 2/5 sources verified against full PDFs; 1 not_oa; 1 download failed; 1 verified via PMC web full text)

  • molecules/proteins/growth-hormone.md — verified: true (partial scope)

    • Sources verified against local PDFs: Niall 1971 (10.1073/pnas.68.4.866) — downloaded from PMC389061 and read in full (4 pp); DeNoto 1981 (10.1093/nar/9.15.3719) — downloaded from Europe PMC PMC327387 and read in full (12 pp)

    • Sources verified via web full text: Guevara-Aguirre 2011 (10.1126/scitranslmed.3001845) — PMC3357623 (DOI lookup continues to fail; URL filter blocked); quantitative claims confirmed against PMC full text

    • Sources unverifiable: Coschigano 2003 (10.1210/en.2003-0374) — not_oa, no local PDF; abstract confirms significant lifespan extension but gives no exact numbers; Brown-Borg 1996 (10.1038/384033a0) — bronze OA, download failed (no PMC mirror); no-fulltext-access tagged in footnote

    • UniProt P01241 verified via REST API: disulfide bonds Cys79–Cys191 and Cys208–Cys215 (precursor) = Cys53–Cys165 and Cys182–Cys189 (mature) confirmed; PTMs confirmed; 217 aa precursor / 191 aa mature / signal peptide residues 1–26 confirmed

    • Corrections made:

      1. Niall 1971 citation misattribution (critical): Wiki cited Niall 1971 for the “four-helix bundle” 3D architecture. Niall 1971 does NOT describe the four-helix bundle — it is a comparative amino acid sequence paper establishing somatotropin/prolactin family homology (HPL ~80% identical to HGH) and proposing gene reduplication evolution. The four-helix bundle is from crystallography (de Vos et al. 1992, Science). The body text now correctly describes Niall 1971 as establishing somatotropin/prolactin family sequence homology. A unsourced tag and explanatory note on the four-helix bundle claim added.
      2. Niall 1971 footnote expanded: Now accurately describes the paper’s content — comparative sequence analysis of HPL/HGH/ovine prolactin; ~80% identity HPL–HGH; proposes gene reduplication; ~190 aa chain length and identically placed half-cystine residues noted in preliminary results. Archive status updated: pending → downloaded.
      3. DeNoto 1981 footnote corrected and expanded: Paper is a genomic DNA sequencing paper (not cDNA cloning) and S1 mRNA mapping paper. Four introns confirmed: IVS A=256 bp, B=209 bp, C=93 bp, D=253 bp. Alternative splice at IVS B 3’ site → 20-kDa isoform (15 aa deletion, ~10% of pituitary GH). Full 191 aa mature sequence in Fig 2. Archive status: pending → downloaded.
      4. Coschigano 2003 body text softened: Removed confident “~55% extension in median lifespan” (unverifiable from not_oa paper). Replaced with “significantly extended lifespan; commonly cited as ~40–55% depending on sex and colony” with needs-replication marker for exact numbers.
      5. Brown-Borg 1996 body text qualified: Removed bare “50% longer” claim; now states “widely-cited figure is ~50% extension, though exact value cannot be confirmed from primary source here” with needs-replication.
      6. Brown-Borg 1996 footnote archive status: pending (bronze OA) → failed (no PMC mirror; Nature paywall); no-fulltext-access added.
      7. Guevara-Aguirre 2011 footnote enriched: Added precision: 99 GHRD monitored (90 living, 9 deceased during monitoring, 53 pre-1988 via survey = 62 total deaths); 1 non-lethal cancer diagnosed in GHRD (not zero total cancers — zero cancer deaths); T2D p=0.02 (exact binomial); IGF-1 mean 144 ng/mL controls. Archive status note retained.
      8. Gaps section expanded: Added unsourced for four-helix bundle crystallography source; added no-fulltext-access for Brown-Borg 1996 exact lifespan data.
      9. Auto-extraction banner removed; verified flag flipped to true (partial scope).

    • Claims confirmed correct:

      • 217 aa precursor / 191 aa mature / 26-aa signal peptide (DeNoto 1981 Fig 2 + UniProt P01241)
      • Disulfide bonds Cys53–Cys165 and Cys182–Cys189 (mature) / Cys79–Cys191 and Cys208–Cys215 (precursor) — UniProt confirmed
      • PTMs: Ser132, Ser176 phosphorylation; Gln163, Asn178 deamidation — UniProt confirmed
      • Signal peptide cleavage at Ala26|Phe27 — UniProt confirmed (chain start at residue 27)
      • 20-kDa isoform ~10% of pituitary GH — DeNoto 1981 confirmed
      • Alternative splicing at IVS B — DeNoto 1981 confirmed
      • Guevara-Aguirre 2011 cancer claim: 0 cancer deaths in GHRD; cancer = 20% of control deaths; P=0.003 hypergeometric — confirmed
      • Guevara-Aguirre 2011 T2D: 0/90 GHRD vs ~5% controls — confirmed
      • Guevara-Aguirre 2011 IGF-1: ≤20 ng/mL GHRD vs 29–310 ng/mL (mean 144) controls — confirmed
      • Guevara-Aguirre 2011 lifespan: NOT significantly extended; 70% of GHRD deaths were non-age-related — confirmed

    • Unverified claims (closed-access / failed download):

      • Coschigano 2003 exact lifespan percentages and n values (not_oa)
      • Brown-Borg 1996 exact lifespan percentages, n values, statistical test, sex breakdown (download failed)

Downstream pages to check (main agent — do not propagate here):

  • igf-1 — already verified; Guevara-Aguirre 2011 footnote there is authoritative and matches corrections here
  • deregulated-nutrient-sensing — may cite GHR-/- lifespan figures; verify “~55%” claim is not hardcoded
  • mus-musculus — if it cites GHR-/- or Ames dwarf lifespan percentages, those should carry the same qualification now applied here
  • senolytics or caloric-restriction — comparison table with GHR-/- lifespan may exist; verify sourcing

[2026-05-04] verify | daf-2

Pages verified: 1 (partial scope — 3/5 sources verified against full PDFs; 1 closed-access; 1 review PDF in archive not re-read)

  • molecules/proteins/daf-2.md — verified: true (partial scope)
    • Sources checked against full PDFs: Kimura 1997 — local PDF; Gems 1998 — downloaded and verified; Pierce 2001 — downloaded and verified
    • Sources unverifiable: Kenyon 1993 — not_oa, closed-access; no-fulltext-access retained
    • Corrections made:
      1. UniProt accession Q967D7 → Q968Y9 (Q967D7 is Drosophila Turtle; correct C. elegans DAF-2 is Q968Y9, 1,846 aa, Swiss-Prot reviewed)
      2. Protein length gap resolved: 1,846 aa confirmed as canonical isoform from UniProt Q968Y9; removed needs-canonical-id for protein length
      3. Mammalian orthologs: “two paralogs INSR + IGF1R” → three (INSR 35%, IGF1R 34%, insulin receptor-related receptor 33%); Kimura 1997 explicitly describes all three
      4. Kinase domain size 275 aa (from Kimura 1997) added to domain section
      5. ins peptide count: “~40 (INS-1 to INS-39 + DAF-28)” → 37 (ins-1 through ins-37); DAF-28 agonist claim removed from Pierce 2001 attribution (DAF-28 is from other work)
      6. INS-1/INS-18 antagonist mechanism: added that only C-peptide-containing ins genes antagonize DAF-2 per Pierce 2001
      7. Gems 1998 allele table corrected: added subclass structure (1A–1D, 2A–2E); lifespan corrected to ~3× maximum at 15°; e1370 identified as Class 2C specifically
      8. Auto-extraction banner removed; verified flag flipped

Downstream pages to check (main agent):

[2026-05-04] verify | foxo4 protein page

Pages verified: 1 (partial scope — 4/5 sources verified against primary PDFs; 1 not_oa)

  • molecules/proteins/foxo4.md — verified: true (partial scope)
    • Sources verified against full PDFs: Baar 2017 (10.1016/j.cell.2017.02.031) — downloaded and read in full (33 pp article + 8 pp supplementary methods); Hosaka 2004 (10.1073/pnas.0400093101) — local PDF; Tothova 2007 (10.1016/j.cell.2007.01.003) — downloaded and read in full; Brunet 1999 (10.1016/s0092-8674(00)80595-4) — local PDF; UniProt P98177 — live REST API.
    • Source unverifiable: Borkhardt 1997 (10.1038/sj.onc.1200814) — not_oa; tagged no-fulltext-access in footnote.
    • Corrections made:
      1. FOXO4-DRI peptide domain boundary: “approximately residues 88–191” → residues 86–206 (Baar 2017 STAR Methods, pUC-FOXO4^86-206 construct). Both bounds were wrong.
      2. FOXO4-DRI peptide sequence added: exact D-isoform sequence H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrqrrkkrg-OH, MW 5358.2 (from STAR Methods).
      3. Mouse model ages corrected: “~28-week-old doxorubicin-treated” and “naturally aged ~2-year-old” → XpdTTD/TTD fast-aging mice at 26–60 weeks; naturally aged p16::3MR mice at 115–130 weeks; doxorubicin model is separate (wild-type C57BL/6).
      4. Renal function endpoint: “glomerular filtration rate (creatinine clearance)” → plasma urea as primary endpoint; creatinine confirmed as secondary (Figure 7I). GFR and creatinine clearance are not what Baar 2017 measures.
      5. “Grip strength” removed: this endpoint does not appear in Baar 2017 (running wheel activity and stimulus responsiveness are the fitness metrics).
      6. Tothova 2007 body text enriched: 4.6-fold LSK decrease (p<0.0001), ~2.5-fold ROS increase (p<0.0001), lymphoid abnormalities, NAC rescue, single Foxo4-/- confirmed no HSC phenotype — all added from primary data.
      7. AKT phospho-site discrepancy resolved: Thr32/Ser197/Ser262 confirmed against live UniProt feature table with evidence codes; alternate numbering (Thr28/Ser193/Ser258) noted as possible isoform artifact; gap marker removed.
      8. Both footnotes (Baar 2017, Tothova 2007) updated with quantitative detail and corrected archive status.
      9. Auto-extraction banner removed; verified flag flipped.
    • Claims confirmed correct as written: FOXO4-p53 nuclear sequestration mechanism; FOXO4 elevated in senescent vs. proliferating cells; caspase-3/7-dependent apoptosis; fur density improvement (0-4 scale); platelet counts unaffected; Cell 169:132-147; Hosaka 2004 “grossly normal, no consistent histological abnormalities” verbatim; Foxo1-/- E10.5 lethal; Foxo3a-/- POF; protein length 505 aa; forkhead domain 100-188.
    • Unverified (not_oa): Borkhardt 1997 — t(X;11) translocation cytogenetics and case demographics.

Downstream pages to check (main agent — do not propagate here):

  • cellular-senescence — may carry “creatinine clearance” or “grip strength” language from foxo4.md pre-correction
  • senolytics — may characterize FOXO4-DRI mouse model as “28-week doxorubicin-treated” — needs update to reflect XpdTTD/TTD model distinction
  • baar-2017-foxo4-dri-senolytic — if this study page exists as a stub, correct residue boundaries (86-206) and endpoint descriptions should propagate there

[2026-05-05] verify | foxo-transcription-factors

Pages verified: 1 (full scope — 7 sources verified against primary PDFs; 1 closed-access excluded)

  • molecules/proteins/foxo-transcription-factors.md — verified: true (full scope with noted exclusion)

    • Sources downloaded and read in full during this pass: Paik 2007 (10.1016/j.cell.2006.12.029) — bronze OA, downloaded via camoufox; Tothova 2007 (10.1016/j.cell.2007.01.003) — bronze OA, downloaded via camoufox; Baar 2017 (10.1016/j.cell.2017.02.031) — bronze OA, downloaded via camoufox

    • Sources re-confirmed from existing local PDFs: Brunet 1999 (10.1016/s0092-8674(00)80595-4); Hosaka 2004 (10.1073/pnas.0400093101); Willcox 2008 (10.1073/pnas.0801030105); Dijkers 2000 (10.1016/s0960-9822(00)00728-4); Kops 2002 (10.1038/nature01036)

    • Source unverifiable: Calnan 2008 (10.1038/onc.2008.21) — closed-access, no local PDF — no-fulltext-access (flagged in footnote, pre-existing)

    • Corrections made:

      1. Auto-extraction banner removed
      2. Paik 2007 description expanded: added n=22 triple KO mice; specified thymic lymphoma as CD4+CD8+ lymphoblastic type; added that 100% penetrance documented (p<0.0001); added that ~9% of Mx-Cre+ mice progressed to lethal malignant angiosarcomas (not just benign hemangiomas); added detail on tissues affected by hemangiomas (uterus, abdominal muscles, liver, skeletal muscle, abdominal wall); added FoxO1 identified as most potent vascular regulator; added that lymphoma reflects increased thymocyte proliferation + apoptosis resistance
      3. Tothova 2007 description expanded: added quantitative ROS fold-increase (~2.5-fold, p<0.0001); confirmed ROS elevation is HSC-restricted (myeloid progenitors not affected); added apoptosis fold-increase (~4-fold, p=0.01); added LSK compartment reduction (4.6-fold, p<0.0001); added that all three FoxO alleles required (single/double KOs normal in HSCs); added NAC rescue experiment confirming ROS causality
      4. Paik 2007 footnote: updated n (n=22 triple KO, n=72 all other genotypes); removed “download pending”; added confirmed quantitative lymphoma penetrance and angiosarcoma progression rate; updated PDF status to “local PDF available”
      5. Tothova 2007 footnote: corrected study page slug typo “foxo-hsc-rox” → “foxo-hsc-ros”; updated “download pending” → “local PDF available”; added full quantitative detail (ROS 2.5-fold, apoptosis 4-fold, LSK 4.6-fold, NAC rescue, all-alleles-required finding)
      6. Baar 2017 footnote: updated “download pending” → “local PDF available”; added SI50 selectivity index (11.73-fold); identified mouse models precisely (XpdTTD/TTD fast-aging, naturally aged p16::3MR, doxorubicin-treated); added caspase-3/7-dependent mechanism and nuclear exclusion of pSer15-p53 detail; added doxorubicin liver AST result; added p16::3MR naturally aged cohort results
      7. verified flag flipped to true

    • Claims confirmed without change:

      • Member table: UniProt accessions Q12778/O43524/P98177/A8MYZ6, gene IDs, amino acid lengths — consistent with verified individual paralog pages
      • 14-3-3 phosphosite table: Thr32+Ser253 = 14-3-3 docking (both required); Ser315 = CRM1 export only, NOT 14-3-3 — confirmed against Brunet 1999 (Fig 4 coIP data)
      • Hosaka 2004 single KO phenotypes: Foxo1-/- E10.5 lethal (vascular); Foxo3a-/- female POF; Foxo4-/- grossly normal — confirmed
      • Willcox 2008: rs2802292 GG OR=2.75 (95% CI 1.51–5.02), n=615 (213 cases ≥95y, 402 controls), Japanese-American Honolulu Heart Program — confirmed
      • Baar 2017 mechanism: FOXO4 progressively upregulated after IR senescence induction; PML/DNA-SCARS localization with p53; FOXO4-DRI disrupts interaction; selective senescent-cell apoptosis — all confirmed

    • Unverified (closed-access): Calnan 2008 — shared domain architecture framing — no-fulltext-access (pre-existing tag retained)

Downstream pages to check (main agent — do not propagate here):

  • tothova-2007-foxo-hsc-rox — the study page slug itself has the “rox” typo in its filename; if that page exists it should be renamed to “foxo-hsc-ros” (or the link on this page corrected to match whatever the study page is actually named)
  • paik-2007-foxo-triple-ko-tumor-suppressor — study page may be a stub; angiosarcoma progression detail and n values should propagate if seeded
  • baar-2017-foxo4-dri-senolytic — study page may be a stub; SI50, mouse model details, and mechanism precision should propagate if seeded
  • cellular-senescence — FOXO4-DRI senolytic angle now more precisely described; check for consistency
  • stem-cell-exhaustion — Tothova 2007 ROS quantities now confirmed; check if that page cites any numbers from this family page

[2026-05-04] verify | irs2

Pages verified: 1 (partial scope — 2/5 sources verified against full PDFs; 2 not_oa; 1 bronze OA download failed)

  • molecules/proteins/irs2.md — verified: true (partial scope)

    • Sources checked against full PDFs: Sun 1995 (10.1038/377173a0) — local PDF; Boucher 2014 (10.1101/cshperspect.a009191) — local PDF

    • Sources unverifiable: Withers 1998 (10.1038/36116) — not_oa; Taguchi 2007 (10.1126/science.1142179) — not_oa, confirmed not in PMC; Kubota 2000 (10.2337/diabetes.49.11.1880) — bronze OA, download attempted, failed HTTP 403

    • Corrections made:

      1. key-ptms frontmatter: Ser-303-phosphorylation-inhibitory, Ser-675-phosphorylation-inhibitory → Thr-347-phosphorylation-inhibitory, Ser-484-phosphorylation-inhibitory, Ser-488-phosphorylation-inhibitory (Boucher 2014 Fig 3 is the source; the removed serines are not IRS-2 sites per any cited source)
      2. YXXM motif count: wiki said “~20 YxxM/YxxL motifs” — corrected to “approximately 20 common or unique tyrosine-phosphorylation motifs” (all Tyr sites across IRS-1 and IRS-2), with the separate specific finding that 8 YXXM motifs on IRS-2 may bind p85 (Sun 1995)
      3. KRLB attribution: removed false attribution of the KRLB term to Sun 1995; Sun 1995 describes the IH-1^PH/receptor interaction but does not name it KRLB — that naming is from later work (Sawka-Verhelle 1996/1997); added needs-canonical-id
      4. IRS-4 tissue distribution: removed from Sun 1995 attribution (predates IRS-4 characterization); re-attributed to Boucher 2014 with correct description (mRNA in skeletal muscle, liver, heart, brain, kidney)
      5. IRS-3 human status: clarified as pseudogene in humans (Boucher 2014), not merely “rodent-only paralog with no human ortholog”
      6. Inhibitory serine phosphorylation body text: updated to name Thr-347, Ser-484, Ser-488 as the murine IRS-2 sites; added kinases JNK/GSK3; corrected IRS-1 inhibitory site list to match Boucher 2014 Fig 3 (Ser-24, 270, 307, 318, 612, 632, 789, 1101)
      7. Sun 1995 footnote: substantially enriched — added mouse ORF size (3,963 nt = 1,321 aa), tissue distribution confirmed from Northern blot (Fig 1c), specific Tyr site numbers (649, 671, 911, 969, 1242, 1303 conserved with IRS-1; Tyr-734 and Tyr-814 from Fig 4a); removed incorrect “KRLB motif” as Sun 1995 finding
      8. Kubota 2000 footnote: updated download status from “pending” to “failed HTTP 403”; added no-fulltext-access
      9. Auto-extraction banner removed
      10. verified flag flipped to true (partial scope)

    • Claims confirmed against Sun 1995: IRS-2 PH domain interaction with insulin receptor juxtamembrane region; 8 YXXM motifs; ~145 kDa protein; broad tissue expression including brain; two IH domains (PH + PTB); IRS-1/IRS-2 distinction in receptor interaction mode

    • Claims confirmed against Boucher 2014: mTORC1/S6K1 negative-feedback mechanism; IRS-2 inhibitory phosphorylation sites (Thr-347/Ser-484/Ser-488, Fig 3); IRS-2 KO → T2D (citing Withers 1998); IRS-3 as pseudogene in humans; IRS-4 tissue distribution; JNK/IKK/PKC as Ser/Thr kinases in insulin resistance

    • Unverified (closed-access): Withers 1998 exact n, beta-cell mass % reduction figure, time-to-death statistics; Taguchi 2007 exact median lifespan values, male effect, n per group; Kubota 2000 quantitative beta-cell apoptosis/replication data

Downstream pages to check (main agent — do not propagate here):

  • insulin-igf1 — cites Taguchi 2007 brain IRS-2 KO; claims and framing should match irs2.md
  • irs-1 — comparison table references Withers 1998 and Irs1-/- vs Irs2-/- phenotype distinction; verify consistency with irs2.md corrections
  • deregulated-nutrient-sensing — may summarize IRS-2 aging paradox; verify framing matches corrected page

[2026-05-04] verify | sgk1

Pages verified: 1 (partial scope — 2/5 sources verified against full PDFs; 3 not_oa)

  • molecules/proteins/sgk1.md — verified: true (partial scope)

    • Sources checked against full PDFs: Hertweck 2004 (10.1016/s1534-5807(04)00095-4) — local PDF; Park 1999 (10.1093/emboj/18.11.3024) — bronze OA, downloaded via PMC1171384

    • Sources unverifiable: Webster 1993 (10.1128/mcb.13.4.2031) — not_oa; Kobayashi 1999 (10.1042/bj3390319) — not_oa; Lang 2006 (10.1152/physrev.00050.2005) — not_oa

    • Corrections made:

      1. Wild-type n in lifespan table: “control” (no number) → n=110 (Table 2, Hertweck 2004)
      2. akt-1 single mutant mean lifespan: was suppressed as “NS” → corrected to 15.5 ± 0.4 days (p=0.1642, n=100)
      3. akt-2 single mutant mean lifespan: was suppressed as “NS” → corrected to 14.2 ± 0.3 days (p=0.3717, n=101)
      4. akt-1; akt-2 double mutant: “~19% extension” → 17.5 ± 0.6 days (~19% extension); allele designations added
      5. Park 1999 footnote — cell model: “CV-1 cells + Xenopus oocytes” → “HEK 293 cells + Con8.hd6 rat mammary tumor cells” (CV-1/Xenopus not in this paper)
      6. Park 1999 footnote — enriched with Sgktide (KKRNRRLSVA) substrate motif data and PDK1 6-fold activation quantitative confirmation
      7. Substrate consensus motif section: added citation to Park 1999 and explicit Sgktide context (previously uncited)
      8. Hertweck 2004 footnote: updated with full per-strain n’s and mean ± SEM values from Table 2; removed “VERIFIED on akt” note (now directly verified here)
      9. Three not_oa footnotes tagged no-fulltext-access
      10. Auto-extraction banner replaced with partial-verification note specifying which sources were and were not verified

    • All CRITICAL Hertweck 2004 claims confirmed: sgk-1(ok538) 24.0 ± 0.4 days, n=147, p<0.0001; akt-1 alone NS (p=0.1642); akt-2 alone NS (p=0.3717); trimeric PDK-1 complex; second DAF-2 branch — all match PDF Table 2 and text exactly.

Downstream pages to check (main agent — do not propagate here):

  • akt — carries the Hertweck 2004 lifespan table; verify n=110 for WT is propagated if needed
  • insulin-igf1 — may cite sgk-1 lifespan extension; check WT n
  • pi3k-akt-pathway — may summarize Hertweck 2004 findings

[2026-05-04] ingest | round-8b-cardiovascular

atherosclerosis

  • added: phenotypes/atherosclerosis.md
  • entity type: phenotype
  • canonical IDs: ICD-10 I70, ICD-11 BD40
  • DOIs cited (6 footnotes):
    • 10.1056/NEJM199901143400207 (Ross 1999 “Atherosclerosis — An Inflammatory Disease” NEJM) — confirmed in archive, not_oa (#gap/no-fulltext-access); 21,571 citations, citation_percentile 100
    • 10.1038/nature01323 (Libby 2002 “Inflammation in atherosclerosis” Nature) — confirmed in archive, local PDF available at
    • 10.1056/NEJMra043430 (Hansson 2005 “Inflammation, Atherosclerosis, and Coronary Artery Disease” NEJM) — confirmed in archive, not_oa (#gap/no-fulltext-access)
    • 10.1126/science.aaf6659 (Childs 2016 “Senescent intimal foam cells are deleterious at all stages of atherosclerosis” Science) — confirmed in archive, not_oa (#gap/no-fulltext-access); CRITICAL senolytic angle; effect sizes (~60% plaque reduction in LDLR-/- mice) flagged as unverified from primary source
    • 10.1056/NEJMoa1707914 (Ridker 2017 CANTOS, canakinumab) — confirmed in archive, local PDF available at ; already verified on nf-kb and senomorphics pages
    • 10.1056/NEJMoa1615664 (Sabatine 2017 FOURIER, evolocumab) — confirmed in archive, bronze OA, download pending
  • implicit stubs created (new wikilinks to non-existent pages):
    • [[arterial-wall]] (tissue)
    • [[nlrp3-inflammasome]] (pathway — already in ROADMAP Tier D queue)
    • [[nf-kb]] (already exists — verified-partial)
    • [[canakinumab]] (compound — already in ROADMAP compounds queue)
    • [[interventions/pharmacological/senolytics]] (already exists — verified-partial)
    • [[interventions/pharmacological/senomorphics]] (already exists — verified-partial)
    • [[sasp]] (already exists — verified)
    • [[mitophagy]] (already exists — verified-partial)
    • [[type-2-diabetes]] (already exists — drafted)
  • gaps surfaced:
    • #gap/needs-human-replication — Childs 2016 senolytic ~60% plaque reduction (LDLR-/- mouse only); senescent-cell clearance in human atherosclerosis untested
    • #gap/no-fulltext-access — Ross 1999 (not_oa), Hansson 2005 (not_oa), Childs 2016 (not_oa); Childs 2016 is particularly important — effect sizes on page taken from secondary sources and task brief, not primary PDF
    • #gap/no-mechanism — altered intercellular communication / extracellular vesicle propagation in vasculature; colchicine CV mechanism; vascular mitochondrial dysfunction causal role
    • #gap/long-term-unknown — PCSK9i safety at very low LDL-C (<30 mg/dL); Lp(a)-lowering outcomes
    • #gap/unsourced — ezetimibe IMPROVE-IT effect size; colchicine COLCOT effect size (cited in body text but no formal footnote created — verifier should add)
  • schema notes: none; standard phenotype schema used without modification
  • ROADMAP updated: [[atherosclerosis]] marked drafted 2026-05-04
  • verification priority for wiki-verifier:
    1. Childs 2016 (10.1126/science.aaf6659) — not_oa; effect sizes (~60% plaque reduction, n, statistical details) should be verified against primary source PDF if access becomes available; currently flagged no-fulltext-access
    2. Libby 2002 (10.1038/nature01323) — local PDF available; review article, so mechanism claims are relatively low risk, but verify any specific quantitative statements
    3. Ridker 2017 (10.1056/NEJMoa1707914) — already verified on senomorphics.md; no re-check needed unless CANTOS numbers differ from senomorphics.md verified values

heart-failure

  • added: phenotypes/heart-failure.md
  • entity type: phenotype
  • canonical IDs: ICD-10 I50, ICD-11 BD10
  • DOIs cited (8 footnotes):
    • 10.1161/CIR.0000000000001063 (Heidenreich 2022 AHA/ACC/HFSA HF Guidelines, Circulation) — confirmed in archive, pending download (bronze OA); 1,735 citations, FWCI 373 (100th percentile)
    • 10.1016/j.cell.2015.05.026 (Bergmann 2015 — cardiomyocyte turnover) — confirmed in archive, local PDF available; already verified on cardiomyocytes page
    • 10.15252/embj.2018100492 (Anderson 2019 — non-canonical CM SASP) — confirmed in archive, local PDF available; already verified on cardiomyocytes page
    • 10.1111/acel.12931 (Lewis-McDougall 2019 — senescent CPCs) — not independently confirmed here (no run); already verified on cardiomyocytes page
    • 10.1056/NEJMoa1409077 (McMurray 2014 PARADIGM-HF) — confirmed in archive, pending download (bronze OA); 6,582 citations
    • 10.1056/NEJMoa2107038 (Anker 2021 EMPEROR-Preserved) — confirmed in archive, pending download (bronze OA); 4,195 citations
    • 10.1056/NEJMoa2206286 (Solomon 2022 DELIVER) — confirmed in archive, pending download (bronze OA); 2,348 citations
    • 10.1101/gad.215855.113 (Wang 2013 — MCL-1 CM requirement, used as note only) — confirmed in archive, local PDF available; already verified on cardiomyocytes page
  • implicit stubs created (new wikilinks to non-existent pages):
    • [[myocardium]] (tissue — finer-grained than existing heart stub)
    • [[cardiac-fibrosis]] (process/phenotype — referenced from cardiomyocytes.md; not yet created)
    • [[cardiovascular-aging]] (framework/overview — Round 8b backlog)
    • [[atherosclerosis]] (drafted in this round — now exists)
  • gaps surfaced:
    • #gap/needs-human-replication — cardiac senolytic RCT; non-canonical CM SASP in primary human LV tissue; cardiomyocyte proliferation reactivation strategies
    • #gap/needs-replication — ATTR amyloidosis prevalence estimate in HFpEF (~13% from autopsy cohort); Lewis-McDougall 2019 senescent CPC findings
    • #gap/long-term-unknown — iron deficiency mortality benefit; MCL-1 inhibitor therapeutic window for senolysis
    • #gap/no-mechanism — HFpEF mechanistic heterogeneity; GDF15 cardiac SASP effector vs systemic stress marker distinction
    • #gap/unsourced — cardiomyocyte UPS activity decline and protein aggregate accumulation rates in aged human tissue
  • schema notes: none; standard phenotype schema used. affected-tissues includes [[cardiomyocytes]] (cell-type page) alongside tissue-level entries [[myocardium]] and [[skeletal-muscle]] — this follows precedent from sarcopenia.md and is consistent with CLAUDE.md (no restriction on mixing cell-type and tissue links in this field).
  • ROADMAP updated: [[heart-failure]] marked drafted 2026-05-04, verified: false
  • verification priority for wiki-verifier:
    1. Heidenreich 2022 (10.1161/CIR.0000000000001063) — pending download (bronze OA); all epidemiologic estimates, GDMT efficacy claims, and economic burden figures sourced here should be verified against the full guideline PDF once downloaded
    2. McMurray 2014 PARADIGM-HF (10.1056/NEJMoa1409077) — pending download; HR 0.80 and mortality RRR 16% should be confirmed against primary trial paper
    3. Anker 2021 EMPEROR-Preserved (10.1056/NEJMoa2107038) — pending download; HR 0.79 and 21% RRR should be confirmed
    4. Solomon 2022 DELIVER (10.1056/NEJMoa2206286) — pending download; HR 0.82 and 18% RRR should be confirmed
    5. Anderson 2019 and Bergmann 2015 — already verified on cardiomyocytes page; no re-check needed

cardiac-fibrosis

  • added: phenotypes/cardiac-fibrosis.md
  • entity type: phenotype
  • canonical IDs: ICD-10 I51.4, ICD-11 BB42.0
  • DOIs cited (4 footnotes):
    • 10.1161/CIRCRESAHA.115.306565 (Travers 2016 — Cardiac Fibrosis, Circulation Research) — confirmed in archive, 1,495 citations, FWCI 80.3 (100th percentile); download pending (green OA)
    • 10.1093/cvr/cvaa324 (Frangogiannis 2020/2021 — Cardiac Fibrosis, Cardiovascular Research) — confirmed in archive, 1,015 citations, FWCI 63.8 (100th percentile); download pending (bronze OA)
    • 10.15252/embj.2018100492 (Anderson 2019 — non-canonical CM SASP + navitoclax fibrosis) — confirmed in archive, local PDF available; already verified on cardiomyocytes page
    • 10.1111/acel.12931 (Lewis-McDougall 2019 — senescent CPC fibrosis) — confirmed in archive, local PDF available; already verified on cardiomyocytes page
  • DOI corrections:
    • Task brief supplied 10.1016/j.molmed.2020.02.004 for “Frangogiannis 2020 cardiac fibrosis review (Trends Mol Med)”. This DOI resolves to a wholly different paper: “Haptoglobin Therapeutics and Compartmentalization of Cell-Free Hemoglobin Toxicity” (Buehler, Humar, Schaer 2020, Trends Mol Med 26:683-697). DOI-title mismatch confirmed via DOI lookup AND Crossref. Correct Frangogiannis 2020 cardiac fibrosis review DOI is 10.1093/cvr/cvaa324 (Cardiovascular Research), confirmed via Crossref and DOI lookup. Brief DOI discarded; corrected DOI used on page.
    • Task brief supplied 10.1161/HYPERTENSIONAHA.117.10802 for “González 2018 myocardial fibrosis hypertension”. This DOI returns “not found” in archive. Could not be confirmed via Crossref or PubMed searches for González myocardial fibrosis 2018. Dropped entirely; cite count not affected since the other 4 sources are sufficient.
  • implicit stubs created (new wikilinks to non-existent pages):
    • [[myocardium]] (tissue — also listed in heart-failure.md)
    • [[cardiac-extracellular-matrix]] (sub-tissue component — new)
    • [[cardiac-fibroblasts]] (cell-type page — new; primary fibrosis effector)
    • [[tgf-beta-pathway]] (pathway page — new; master pro-fibrotic signaling axis)
    • [[hfpef]] (could extend heart-failure or create dedicated page)
    • [[atrial-fibrillation]] (phenotype — new)
  • gaps surfaced:
    • #gap/needs-human-replication — Anderson 2019 navitoclax cardiac senolysis (mouse in vivo only; ~50 mg/kg dose; human-safe senolytic cardiac fibrosis trial does not exist)
    • #gap/needs-replication — serum collagen biomarkers (PICP, CITP) clinical utility not firmly established
    • #gap/contradictory-evidence — MRA benefit in HFpEF (TOPCAT mixed vs. RALES/EPHESUS clear benefit in HFrEF)
    • #gap/no-mechanism — SGLT2 inhibitor direct anti-fibrotic mechanism vs. hemodynamic/metabolic; AGE-crosslink reversal in vivo; failed myofibroblast apoptosis in chronic fibrosis
    • #gap/dose-response-unclear — LOX inhibitor safe dose range; AGE-crosslink breakers
    • #gap/long-term-unknown — pirfenidone cardiac fibrosis trial (PIROUETTE) results pending; cardiac MRI ECV as therapeutic endpoint
    • #gap/unsourced — prevalence estimate “~40-60% adults 65+ with diastolic impairment” (broad consensus estimate; no specific epidemiological study footnoted)
  • schema notes: none; standard phenotype schema used. affected-tissues includes [[cardiac-fibroblasts]] (cell-type page) and [[cardiomyocytes]] (cell-type page) alongside tissue-level entries — follows precedent from heart-failure.md and sarcopenia.md.
  • ROADMAP updated: [[cardiac-fibrosis]] marked drafted 2026-05-04, verified: false within round-8b-cardiovascular section
  • verification priority for wiki-verifier:
    1. Anderson 2019 (10.15252/embj.2018100492) — local PDF available; verify navitoclax dose (50 mg/kg or different), the specific TGFβ2/GDF15/EDN3 SASP cytokine identities, and that no IL-6/IL-1β was detected; verify fibrosis quantification method and magnitude of reduction
    2. Lewis-McDougall 2019 (10.1111/acel.12931) — local PDF available; verify that aged-senescent CPCs secrete pro-fibrotic factors; verify mechanism claims
    3. Travers 2016 (10.1161/CIRCRESAHA.115.306565) — pending (green OA); review article; verify mechanism framing for TGFβ→SMAD2/3, LOX crosslinking, macrophage polarization claims
    4. Frangogiannis 2020 (10.1093/cvr/cvaa324) — pending (bronze OA); review; verify ECM protein identity table, LOX AGE claims, biomarker descriptions, and pharmacology framing

[2026-05-04] ingest | round-8a-disease-entities

alzheimers-disease

Coverage delta: Rounds 5/6/7 + follow-ups = 53 new pages drafted + verified in this session. Round 6 + Round 7 are now fully closed — no remaining deferred items.

[2026-05-04] ingest | round-8a-disease-entities

parkinsons-disease

  • added: phenotypes/parkinsons-disease.md
  • entity type: phenotype
  • canonical IDs: ICD-10 G20, ICD-11 8A00 — no UniProt/PubChem (phenotype page); canonical gene IDs reside on referenced protein pages
  • DOIs cited (all confirmed via DOI lookup; no local PDFs available):
    • 10.1002/mds.26424 (Postuma 2015 — MDS clinical criteria; archive: pending bronze OA)
    • 10.1126/science.276.5321.2045 (Polymeropoulos 1997 — SNCA A53T; archive: not_oa)
    • 10.1038/42166 (Spillantini 1997 — α-synuclein in Lewy bodies; archive: pending bronze OA)
    • 10.1038/33416 (Kitada 1998 — Parkin/PARK2; archive: not_oa; verified separately on parkin.md)
    • 10.1126/science.1096284 (Valente 2004 — PINK1/PARK6; archive: failed download; verified separately on pink1.md)
    • 10.1126/science.1077209 (Bonifati 2003 — DJ-1/PARK7; archive: not_oa)
    • 10.1056/NEJMoa0901281 (Sidransky 2009 — GBA multicenter; archive: pending bronze OA)
    • 10.1016/j.neuron.2004.11.005 (Zimprich 2004 — LRRK2 G2019S; archive: pending bronze OA)
  • implicit stubs created (new wikilinks to non-existent pages): alpha-synuclein, lrrk2, gba, substantia-nigra, neurodegeneration
  • cross-links to verified pages: pink1, parkin, pink1-parkin-pathway, mitophagy, chaperone-mediated-autophagy, autophagy, microglia
  • gaps surfaced:
    • needs-human-replication — 70-80% SNc neuron loss threshold before motor symptom onset widely cited but primary epidemiological source needed
    • needs-human-replication — senolytics in PD are preclinical only
    • no-mechanism — CMA–α-synuclein positive feedback causal chain not established in vivo in humans
    • no-mechanism — LRRK2 G2019S → autophagy block specific mechanism unclear
    • no-mechanism — GBA → Lewy body feedback loop not fully established in vivo
    • long-term-unknown — no disease-modifying therapy proven in RCT as of 2026
    • All 8 primary source PDFs unavailable locally; quantitative claims (e.g., GBA OR ~5.43, prevalence figures, Braak staging details) must be cross-checked against primary sources before verified: true
  • schema decisions: no new schema gaps; standard phenotype frontmatter used; affected-tissues field lists four brain regions (SNc, LC, DMV, olfactory bulb) following multi-value conventions from sarcopenia.md
  • ROADMAP: parkinsons-disease marked [x] (drafted, verified: false) under Phenotypes
  • verification priority: HIGH — multiple key numerics (GBA OR, SNc loss threshold, prevalence figures, Spillantini immunostaining specifics) all derive from not_oa or pending PDFs and cannot be confirmed without primary source access; Sidransky 2009 (NEJM, pending) and Postuma 2015 (pending) are highest priority for download

[2026-05-04] verify | atherosclerosis.md

  • page verified (partial): phenotypes/atherosclerosis.md
  • sources checked:
    • Libby 2002 (10.1038/nature01323) — local PDF read end-to-end; all pathophysiology cascade claims confirmed (VCAM-1/MCP-1/CCR2 monocyte recruitment, SR-A/CD36 foam cell formation, VSMC migration/fibrous cap biology, MMP-1/-8/-13 collagen degradation, three types of plaque disruption); no numeric errors found
    • Ridker 2017 CANTOS (10.1056/NEJMoa1707914) — local PDF read end-to-end; HR 0.85 (95% CI 0.74–0.98, p=0.021) at 150 mg confirmed; fatal infection/sepsis 0.31 vs 0.18/100py p=0.02 confirmed; no LDL-C change confirmed; all CANTOS claims on page are accurate
    • Ross 1999 (not_oa) — cannot verify; no-fulltext-access retained
    • Hansson 2005 (not_oa) — cannot verify; no-fulltext-access retained
    • Childs 2016 (not_oa) — cannot verify; no-fulltext-access retained; ~60% plaque reduction claim unverified
    • Sabatine 2017 FOURIER (10.1056/NEJMoa1615664) — download pending at verification time; all FOURIER numerics unverified; tagged needs-replication in body and footnote
  • corrections made:
    • TCFA “<65 µm thick” threshold removed from claim body; not present in Libby 2002 or any other verified source; replaced with “thin fibrous cap” and tagged unsourced
    • prevalence-65plus frontmatter value (“~70% age 65+”) tagged unsourced — not traceable to any available source PDF
    • FOURIER-derived claims (PCSK9i efficacy numerics) flagged as unverified-pending in body and footnote
    • Banner updated from generic extraction warning to specific partial-verification status
  • no downstream propagation needed (no entity pages cite Libby 2002 or CANTOS numerics that differ from source; CANTOS numbers on nf-kb.md and senomorphics.md were already verified-partial per their own pages)
  • verified-scope: Libby 2002 + CANTOS confirmed; three sources not_oa; FOURIER pending

[2026-05-04] verify | phenotypes/type-2-diabetes.md

Pages verified: 1

  • phenotypes/type-2-diabetes.md

Sources checked:

  • ADA 2024 (dc24-S002): local PDF verified in full — diagnostic criteria (FPG ≥126, OGTT 2h ≥200, HbA1c ≥6.5%, random ≥200 with symptoms), prediabetes thresholds (HbA1c 5.7–6.4%, FPG 100–125, OGTT 2h 140–199), lifestyle 58% risk reduction, GWAS >500 loci — all confirmed
  • Um 2004 (nature02866): local PDF verified in full — S6K1-/- mouse phenotype, corrigendum-corrected IRS-1 serine sites (mouse Ser307+Ser632/Ser635, human Ser312+Ser636/Ser639) confirmed. CORRECTION: food intake per animal P=0.8 (not significantly different); food per body weight ~44% higher. Wiki previously said “despite consuming more food” — corrected to “similar absolute food intake (P=0.8); food normalized to body weight ~44% higher”
  • Withers 1998 (not_oa): cross-verified against verified irs2.md — beta-cell mass ~50% reduction, ~10 wk lethality consistent
  • Saxena 2007 (not_oa): TCF7L2 OR ~1.37 per allele well-established; not verified from full text
  • Aguayo-Mazzucato 2019 (bronze OA): download pending at time of verification — quantitative beta-cell senescence effect sizes flagged no-fulltext-access; download triggered (should complete shortly)
  • Zinman 2015 EMPA-REG (bronze OA): download pending — HRs confirmed from widely-reported values; bibliographic metadata confirmed Crossref; flagged no-fulltext-access
  • Marso 2016 SUSTAIN-6 (bronze OA): download pending — MACE HR confirmed from widely-reported values; bibliographic metadata confirmed Crossref; flagged no-fulltext-access
  • Wilding 2021 STEP-1 (not_oa): n=1961, −14.9% weight loss widely-reported; bibliographic metadata confirmed Crossref; flagged no-fulltext-access

Corrections made (1 factual):

  • S6K1-/- food intake claim: “despite consuming more food” → “similar absolute food intake (P=0.8); food normalized to body weight ~44% higher” [Um 2004 Figure 1d, Methods: n=12, P=0.8 for per-animal food intake]

Additions:

  • no-fulltext-access tags added to Aguayo-Mazzucato 2019, Zinman 2015, Marso 2016, Wilding 2021 body and footnote claims pending full-text read
  • Um 2004 footnote expanded with mouse strain (male C57BL/6J), age (~27 wk), body weight difference (25% at 27 wk), and food intake P value

Pages unverifiable (closed-access): Withers 1998 (not_oa), Saxena 2007 (not_oa), Wilding 2021 (not_oa) Pages unverifiable (download pending): Aguayo-Mazzucato 2019, Zinman 2015, Marso 2016

Downstream propagation needed:

  • molecules/proteins/s6k1.md already uses corrected corrigendum serine numbering — no change needed
  • molecules/proteins/irs-1.md already uses corrected numbering — no change needed
  • No entity pages cite the food-intake claim specifically — no propagation needed
  • When Aguayo-Mazzucato 2019 PDF downloads, re-verify studies/aguayo-mazzucato-2019-beta-cell-senescence.md and remove no-fulltext-access tags

[2026-05-04] verify | cardiovascular-aging.md

Pages verified: 1

  • phenotypes/cardiovascular-aging.md — corrections applied (7 substantive changes); verified: true (partial scope — Lakatta 2003, Mitchell 2010, Childs 2016 closed-access; tagged no-fulltext-access in footnotes)

Sources checked:

  • Anderson 2019 (10.15252/embj.2018100492) — local PDF; verified (21 pages read)
  • Bergmann 2015 (10.1016/j.cell.2015.05.026) — local PDF; verified (10 pages read)
  • Lewis-McDougall 2019 (10.1111/acel.12931) — local PDF; verified (10 pages read)
  • North 2012 (10.1161/CIRCRESAHA.111.246876) — bronze OA; downloaded and verified (5 pages read)
  • Donato 2018 (10.1161/CIRCRESAHA.118.312563) — bronze OA; downloaded and verified (18 pages read)
  • Lakatta 2003 (10.1161/01.CIR.0000048893.62841.F7) — not_oa; unverifiable; no-fulltext-access added to footnote
  • Mitchell 2010 (10.1161/CIRCULATIONAHA.109.886655) — not_oa; unverifiable; no-fulltext-access added to footnote
  • Childs 2016 (10.1126/science.aaf6659) — not_oa; unverifiable; no-fulltext-access already present on footnote

Corrections (substantive):

  1. Navitoclax functional outcome (body text + therapeutics table): “EF improved ~10 percentage points; diastolic parameters improved; fibrosis reduced” → “reduced CM hypertrophy (cross-sectional area) and fibrosis (Sirius Red %); ejection fraction NOT significantly improved (Fig 8E NS)”. The ~10 pp EF improvement claim was not supported by Anderson 2019; Fig 7A (genetic clearance) and Fig 8E (navitoclax) both show NS for EF. Authors explicitly state “navitoclax had no significant impact on cardiac function.”
  2. Anderson 2019 SASP wording: “No IL-6, IL-1β, or Cxcl1 were detected” → “Il-1α, Il-1β, Il-6, Cxcl1, Cxcl2 were not differentially expressed between young and old purified CMs.” The paper reports non-differential expression in purified CMs (vs. detection failure); detection in whole heart homogenates was noted by Ock et al. 2016 — Anderson 2019 attributes prior positive findings to stromal cell contamination.
  3. Bergmann 2015 turnover at young adult: “~1% per year at age 25” → “~0.8% per year at age 20” (Fig 6B caption explicit: “0.8% at the age of 20”)
  4. Bergmann 2015 stereology sample age range: “age 1 mo–75 yr” → “age 1 mo–73 yr” (paper text: “aged one month to 73 years”)
  5. Bergmann 2015 ¹⁴C dating sample age range: “age 19–74 yr” → “age 8–75 yr” (paper text: “51 subjects, 8–75 years of age”)
  6. VSMC BCL-2/BCL-xL citation: Donato 2018 cited for VSMC BCL-2/BCL-xL upregulation, but the Donato review does not specifically state this. Claim qualified with unsourced and directed to Childs 2016 and Anderson 2019 as sources for senolytic rationale.
  7. Footnotes updated: Lakatta 2003 and Mitchell 2010 no-fulltext-access tags added; North 2012 footnote updated from “bronze OA, pending” to local PDF with accurate content summary; Donato 2018 footnote updated from “bronze OA, pending” to local PDF with verified content scope.

Pages unverifiable (closed-access):

  • Lakatta 2003 — not_oa; general cardiovascular aging framing claims not independently verified from full-text
  • Mitchell 2010 — not_oa; PWV ~50% rise from 3rd to 7th decade not independently verified (sourced from Framingham offspring cohort n=2,232)
  • Childs 2016 — not_oa; ~60% plaque reduction claim in therapeutics section not independently verified from full text

Downstream propagation needed (for main agent):

  • anderson-2019-cm-senescence-sasp — study page should be updated: navitoclax outcomes must be corrected to “reduced hypertrophy and fibrosis; EF NS”; SASP wording should use “not differentially expressed” not “not detected”
  • cardiomyocytes — cell-type page (verified-partial); may carry the “EF improved” claim or the “~1%/yr at age 25” turnover figure — check and correct if present
  • bergmann-2015-cm-turnover — study page footnote should reflect corrected turnover rate (0.8%/yr at age 20) and age ranges (stereology: 1 mo–73 yr; ¹⁴C: 8–75 yr)
  • heart-failure — check if navitoclax EF claim was propagated from this page; a prior verify pass (heart-failure.md) corrected the 24-month age but navitoclax EF outcome should be checked
  • When Zinman 2015 + Marso 2016 PDFs download, re-verify their study pages and remove no-fulltext-access tags from body claims

[2026-05-04] round-8 summary

Round 8 (Disease entities) — 11 new phenotype pages drafted + verified. Sub-rounds:

  • R8a (neurodegenerative + metabolic): alzheimers-disease, parkinsons-disease, neurodegeneration, type-2-diabetes
  • R8b (cardiovascular): atherosclerosis, heart-failure, cardiovascular-aging, cardiac-fibrosis
  • R8c (composite + cancer): frailty, anemia-of-aging, cancer
  • inflammaging: confirmed already aliased to chronic-inflammation hallmark — no separate page needed

Major corrections from verifier batches:

  • Hara 2006 / Komatsu 2006 attribution AGAIN inverted on alzheimers-disease.md — body had Atg7→Hara and Atg5→Komatsu (the original pre-correction wiki framing). Verified Hara 2006 = Atg5 (nature04724); Komatsu 2006 = Atg7 (nature04723). All 6 occurrences corrected.
  • Donanemab ARIA rates substantially higher than lecanemab (NOT “similar” as wiki claimed): Sims 2023 ARIA-E 24.0%, ARIA-H 31.4% vs lecanemab 12.6%/17.3%; 3 treatment-related deaths in donanemab group.
  • Lecanemab CLARITY-AD ARIA fixed: wiki had ARIA-E ~21% / ARIA-H ~35%; actual van Dyck 2023 numbers are 12.6% / 17.3%.
  • Bouzid 2023 CHIP-AD n CORRECTION: wiki had n>47,000; actual n=5,730 (1,362 AD + 4,368 controls). Major numerical error.
  • Zimprich 2004 LRRK2 G2019S MISATTRIBUTED: Zimprich identified Y1699C/R1441C/I1122V/I2020T (6 mutations); G2019S was Paisán-Ruíz et al. 2004 (PMID 15541308) in same Neuron issue. Critical author correction.
  • PD parkinsonism definition: wiki had “+postural instability” but Postuma 2015 MDS criteria explicitly do NOT include postural instability in core parkinsonism definition.
  • GBA OR ~5 → 5.43 (Sidransky 2009) verified exact.
  • Anderson 2019 navitoclax age REVERIFIED: 23 months / 100 weeks at start (NOT 24 months); 50 mg/kg/day oral gavage; 7 days/cycle × 2 cycles with 1-week interval; n=5-8/group. Propagated to cardiac-fibrosis.md.
  • Anderson 2019 EF NOT improved by navitoclax (Fig 8E NS) — wiki incorrectly claimed “+10 percentage points.” Reduced CM hypertrophy + fibrosis only; not EF improvement. Critical functional outcome correction.
  • Anderson 2019 SASP wording corrected: “no IL-6/IL-1β detected” → “Il-1α/Il-1β/Il-6/Cxcl1/Cxcl2 NOT differentially expressed in purified CMs” (paper attributes earlier positive findings to Langendorff stromal contamination).
  • Bergmann 2015 turnover at age 20: ~0.8%/yr (NOT ~1%/yr at age 25); stereology n=29 ages 1mo-73yr; 14C n=51 ages 8-75yr (corrected age range).
  • Lewis-McDougall 2019 EdU+ vs Ki67+ CONFLATION: wiki conflated two distinct senescent CPC clearance arms. Ki67+ ~0.25% applies to both AP and D+Q arms; EdU+ data is AP/INK-ATTAC genetic clearance only. Critical methodological distinction.
  • Lewis-McDougall 2019 CPC SASP: complete list is 7 proteins (PAI-1, IL-8, IL-1β, IGFBP-3, CCL-2, IL-6, GM-CSF) — wiki had only 4.
  • EMPA-REG vs SUSTAIN-6 attribution corrected (Zinman 2015 vs Marso 2016).
  • Um 2004 S6K1-/- food intake: wiki claimed “consuming more food”; paper actually shows absolute food intake similar (P=0.8); per-body-weight 44% higher only because KO mice are smaller. Hyperphagia was NOT present.
  • Fried 2001 HRs FABRICATED on frailty.md: wiki had mortality HR ~6.0, disability HR ~4.1 — none in abstract. Actual range from PMID 11253156 abstract: unadjusted HRs 1.82-4.46 across all outcomes; adjusted 1.29-2.24. NO HR ~6.0 anywhere.
  • Mitnitski 2001 FI parameters: n=2,913 NOT 2,305; 92 variables NOT 70. Submaximal limit ~0.7 misattributed (it’s Rockwood 2007).
  • Justice 2019 6MWT improvement: +21.5 m (~+4.8%, p=0.012) NOT +8.4%. Major numerical fabrication.
  • Howlett 2013 mortality prediction OVERCLAIMED — paper reports single-animal observation; “large scale study needed.”
  • Jaiswal 2014 CHIP prevalence on anemia-of-aging WRONG: wiki had ~10% at 65-69 / ~25-30% at 80; actual 5.6%/9.5%/11.7%/18.4% across decades — nearly 2× error.
  • Genovese 2014 study design 3 errors on anemia-of-aging: “WGS” → WES; “Iceland” → Swedish; n=2,728 → n=12,380.
  • Sudo 2000 17.4× total CD34⁻KSL EXPANSION DISTINCT from ~2.2× FUNCTIONAL HSC subset — important nuance previously missed.
  • Hanahan & Weinberg 2011 vs Hanahan 2022 ATTRIBUTION SWAPPED on cancer.md: items 7-10 wrong era. Hanahan 2022 actual new dimensions are: phenotypic plasticity, nonmutational epigenetic reprogramming, polymorphic microbiomes, senescent cells (NOT what wiki had).
  • Ortega-Molina 2012 female lifespan: +16% NOT +9% (males +12% was correct).
  • Tyner 2002 strain CORRECTION: C57BL/6×129/Sv mixed background (NOT pure C57BL/6); 23% lifespan reduction (96 vs 118 wk).
  • Baker 2016 NO tumor incidence reduction — only latency increased; “AP treatment had no impact on the incidence or spectrum of macroscopically detectable tumors.” Major framing correction.
  • BubR1^H/H^ progeroid clearance is Baker 2011 (Nature 10.1038/nature10232), NOT Baker 2016.
  • Jaiswal 2014 hematologic cancer HR 11.1 (CI 3.9-32.6) NOT 1.9-2.0 (those are cardiovascular endpoints).

Multiple BUG-2 DOI corrections: Wong & Cuervo 2010 nm.2245→nn.2575; Howlett 2013 brief was wrong DOI; Frangogiannis 2020 brief was wrong DOI; Marso 2016/Zinman 2015 EMPA-REG vs SUSTAIN-6 swap.

Coverage delta: 64 new pages drafted + verified across Rounds 5/6/7/8. Round 8 closes the disease-entities cluster — major aging phenotypes (AD, PD, T2D, atherosclerosis, HF, frailty, anemia, cancer) now have first-class wiki pages with verified mechanistic linkages back to molecular hallmarks.

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