2026-06-26

[2026-06-26] ingest | senolytics x muscle hypertrophy

• added: studies/dungan-2022-senolytic-muscle-hypertrophy.md
• doi: 10.1007/s11357-022-00542-2 · PMID 35325353 · PMC9616988 (open access)
• study design: in-vivo (aged mouse MOV) + partial human arm (biopsy IHC)
• key findings captured: exercise-induced senescence in human + mouse muscle; amplified burden in old mice; D+Q hit-and-run rescues hypertrophy; Igf1/Ddit4/Mmp14 gene changes
• cross-links resolved: dasatinib, quercetin, satellite-cells, skeletal-muscle, sarcopenia, cellular-senescence, p21, igf-1, senolytics, fisetin (background only)
• implicit stubs created: mmp14, ddit4 (REDD1), muscle-hypertrophy (process), synergist-ablation (method)
• gaps flagged: n per group from abstract only (#gap/needs-n-per-group-from-pdf); fiber-type CSA direction for Ddit4/Mmp14; sex-only male mice; single-lab; no human RCT of D+Q + resistance training (#gap/needs-human-replication)
• verified: false — verifier pass pending (PMC9616988 is OA; full PDF accessible)

[2026-06-26] verify | dungan-2022-senolytic-muscle-hypertrophy

• verified: studies/dungan-2022-senolytic-muscle-hypertrophy.md → verified: true
• source read: PMC9616988 full PDF (16 pages, all sections)
• corrections applied:
  • human arm: n added (18 subjects — 10M+8F, age 20–39 yr, not “extractable from abstract”)
  • mouse strain: C57BL/6 → C57BL/6J; old mouse body weight added (33.0±2.6 g vs 29.8±1.8 g adult)
  • n per group: MOV time-course N=6–8/group; senolytic arm N=7–9/group; RNA-seq N=5/group
  • human biopsy timing: “~2 weeks” confirmed as “approximately 14 days”
  • fiber-type specificity: type 2a hypertrophy is NOT selectively blunted (both ages enlarge type 2a); blunting is specific to type 2x+2b; type 1 not independently quantified
  • D+Q rescue: selectively rescues type 2x+2b CSA; type 2a enlarged in both vehicle- and D+Q-MOV groups
  • Ddit4 direction: “altered” → downregulated (confirmed from Fig. 6b violin plot + text)
  • Mmp14 direction: “altered” → upregulated (confirmed from Fig. 6c violin plot + text)
  • Added: ~2,000 DEGs total; no hallmark SASP inflammatory gene changes detected; Adamts1/Plau/Cryab also highlighted DEGs; ECM remodeling and TCA pathway summaries; D+Q mechanism discussion (M2 macrophage Mmp14 source caveat)
• gaps closed: n per group, fiber-type direction for rescue, Ddit4/Mmp14 directions, human biopsy n and timing
• gaps remaining: canonical synergist-ablation reference (#gap/needs-canonical-ref-synergist-ablation); no human RCT of D+Q+resistance training (#gap/needs-human-replication); male-only sex limitation noted
• supersession check: PubMed search (2022–2026): no meta-analysis or RCT on D+Q + muscle hypertrophy found; one follow-on mouse study (PMID 37872294, BI01 senolytic, GeroScience 2024) consistent with Dungan framing — not superseding
• literature-checked-through: 2026-06-26

[2026-06-26] ingest | senolytics × muscle hypertrophy (Moiseeva 2023)

• added: studies/moiseeva-2023-senescence-atlas-muscle-regeneration.md
• doi: 10.1038/s41586-022-05535-x · PMID 36544018 · PMC9812788 (CC BY 4.0 — open access)
• author correction noted: doi:10.1038/s41586-023-05765-7 (2023-02-06); flagged in page for verifier review
• study design: in-vivo (mouse cardiotoxin muscle injury + human biopsy confirmation)
• organism: multi (mus-musculus primary; homo-sapiens biopsy confirmation)
• key findings captured: senescent-cell enrichment atlas via scRNA-seq; inflammation + fibrosis as universal hallmarks; aged-like inflamed niche arrests satellite-cell proliferation; senescent-cell clearance OR CD36 neutralization accelerates regeneration in young + old mice; transplant delays regeneration; human muscle senescent-cell accumulation confirmed
• cross-links resolved: cellular-senescence, sasp, satellite-cells, skeletal-muscle, senolytics, chronic-inflammation, sarcopenia
• implicit stubs created: cd36 (proteins/), inflammaging (phenotypes/)
• gaps flagged: n per group from abstract only; correction impact not assessed; human intervention data absent (#gap/needs-human-replication); single-lab (#gap/needs-replication); CD36 specificity not assessed
• verified: false — verifier pass pending (PMC9812788 is OA; full PDF + correction accessible)

[2026-06-26] verify | moiseeva-2023-senescence-atlas-muscle-regeneration

• verified: studies/moiseeva-2023-senescence-atlas-muscle-regeneration.md → verified: true
• sources read: PMC9812788 full PDF (14 pages + methods, all sections); Author Correction PMC9946821 (1 page)
• author correction impact: nil — purely a name-hyphenation fix (Salvador “Aznar-Benitah” → “Aznar Benitah”); zero scientific content affected
• corrections applied:
  • mouse strains: “C57BL/6 mice” → C57BL/6 WT + p16-3MR reporter (C57BL/6 background) + mdx/p16-3MR (DBA/2) for chronic-damage arm; strain identity is central to experimental design
  • human biopsy n and demographics: filled from Methods (n=5 samples; female; ages 69, 82, 80, 89, 85 yr; mean 81±7.5 yr; vastus lateralis; EU/FP7 Myoage Consortium biobank)
  • scRNA-seq atlas size: added “21,449-cell” count from Fig. 1f legend
  • SPiDER enrichment specificity: 93.6% enriched in senescent cells (Extended Data Fig. 1g) added
  • senescent cell types: three identified (MCs ≥ FAPs > SCs in order of abundance) + smaller populations named; prior text vague on identity
  • SASP component range: 78–363 components per cell type/condition added (Extended Data Fig. 10a)
  • hallmark universality definition: clarified as FDR <0.25 in at least 8 of 12 comparisons; 47 universal DEGs noted
  • key SASP genes named: Ccl2, Ccl7, Ccl8, Isg15 (inflammatory); Col3a1, Col6a2, Timp2 (fibrotic)
  • senescent-cell transplant n: 10,000 cells/TA (5,000 when individual types); n=4 mice per group added
  • CD36 terminology: “fatty acid translocase” → “scavenger receptor related to lipid metabolism” (paper’s own language, Discussion p.177)
  • CD36 mechanism: clarified that CD36 blockade does NOT reduce senescent cell number (Fig. 6d) — acts as senomorphic by reducing SASP proteins; Cd36-siRNA transplant rescue confirmed specificity
  • D+Q doses: dasatinib 5 mg/kg + quercetin 50 mg/kg oral (gavage); GCV 25 mg/kg i.p. added
  • anti-CD36 doses: 10 μg (young) / 20 μg (old), i.p., 4 days starting at 3 d.p.i. added
  • human confirmation scope clarified: SA-β-gal + CDKN2A IHC only; PAX7+/PDGFRα+/CD68+ 53BP1+ cells in damaged human muscle also noted
  • limitations section: restructured to close gaps now addressable from PDF; added specificity of strain limitation, SPiDER contamination caveat; retained gap/needs-human-replication and gap/needs-replication
• supersession check (2023–2026):
  • 9 hits for “senescent cells skeletal muscle regeneration senolytic” post-2023
  • PMID 40617829 (Nat Commun 2025, doi:10.1038/s41467-025-61403-y): first snRNA-seq senescence atlas of aging HUMAN skeletal muscle; identifies Maraviroc as senotherapeutic for sarcopenia; COMPLEMENTS (extends to human tissue) rather than supersedes Moiseeva 2023 — consistent framing, distinct targets
  • PMID 42069587 (Skeletal Muscle 2026): DMD mdx senescence dynamics + therapeutic windows — consistent with Moiseeva; no supersession
  • PMID 37872294 (GeroScience 2024): p53-MDM2 inhibitor senolytic in aged mice — consistent; no supersession
  • No meta-analysis or large RCT on CD36 neutralization or senescent cells in muscle regeneration found
• literature-checked-through: 2026-06-26
• supersession flag: PMID 40617829 (Nat Commun 2025) flagged as follow-on candidate for seeding as separate study page (first human snRNA-seq senescence atlas + Maraviroc senotherapeutic)

[2026-06-26] ingest | senolytics × muscle hypertrophy (Murray 2025 fisetin)

• added: studies/murray-2025-fisetin-muscle-function.md
• doi: 10.1111/acel.70114 · PMID 40437670 · PMC12341784 (gold OA, CC BY 4.0 — full text available for verifier)
• study design: in-vivo (aged and young mice; intermittent oral fisetin vs genetic p16-3MR clearance vs intermittent navitoclax/ABT-263)
• key findings captured: fisetin mitigates age-related frailty + grip strength decline in old mice; no effect in young mice; quadriceps RNA-seq shows lower Cdkn1a/p21 and Ddit4 abundance; functional gains comparable to p16-3MR genetic clearance and ABT-263
• cross-links resolved: fisetin, navitoclax, cellular-senescence, skeletal-muscle, sarcopenia, frailty, satellite-cells, senolytics, p21, yousefzadeh-2018-fisetin-senolytic, dungan-2022-senolytic-muscle-hypertrophy
• implicit stubs created: ddit4 (REDD1/Ddit4 protein page does not exist), cdkn1a (Cdkn1a gene page does not exist — p21 page exists but not cdkn1a)
• pages NOT found: processes/cellular-senescence.md (hallmarks/cellular-senescence.md used instead); molecules/proteins/cdkn2a.md (p16 — no page); molecules/proteins/ddit4.md (no page, stub flagged)
• critical gap flagged: abstract reports TRANSCRIPTOMIC senescence readout (Cdkn1a/Ddit4 mRNA lower) but does NOT clearly state whether direct senescent-cell-count data (SA-β-gal, p16-IHC) in muscle was obtained; verifier must confirm from full PDF (PMC12341784); n per group, doses, mouse strain/age, and exact p-values also require full-text extraction
• verified: false — verifier pass required; PMC12341784 is OA gold, full text accessible

[2026-06-26] verify | murray-2025-fisetin-muscle-function

• page: studies/murray-2025-fisetin-muscle-function.md
• source: doi:10.1111/acel.70114 · PMC12341784 · full 15-page PDF read end-to-end
• verified: true
• corrections made:
  • n-subjects frontmatter: null → 98 (fisetin arm total: YV=9, YF=11, OV=31, OF=39); p16-3MR and ABT-263 arms are separate studies
  • strain/age: added C57BL/6N wildtype + C57BL/6 background p16-3MR; young 6–8 months, old males 27 months, old females 29 months
  • dose (fisetin): not stated in abstract → 100 mg/kg/day oral gavage (vehicle: 10% EtOH, 30% PEG400, 60% Phosal 50 PG)
  • dose (ABT-263): not stated → 50 mg/kg/day oral gavage same vehicle, same schedule
  • GCV dose/route: 25 mg/kg/day IP × 5 consecutive days
  • frailty effect sizes: now populated with exact values (Old Veh 0.27±0.01 AU; Old Fisetin 0.23±0.01 AU; 15% lower; p=0.0264)
  • grip strength effect sizes: Old Veh 2.90±0.1 g/g BW; Old Fisetin 3.30±0.1 g/g BW; 14% higher; p=0.0038
  • aging-effect attenuation: frailty 18%; grip strength 40%
  • comparator statistical form: clarified as “no significant difference between groups” (p=0.83–0.99) NOT formal non-inferiority test; ABT-263 numerically larger effect
  • CRITICAL senescence readout: confirmed NO SA-β-gal, NO p16/p21 IHC cell counting, NO flow cytometry in muscle; readout is exclusively transcriptomic (bulk RNA-seq + RT-PCR); TL;DR, Key Results, and Limitations updated explicitly
  • fisetin did NOT reduce Cdkn2a (p16) in muscle (only Cdkn1a/p21 and Ddit4); ABT-263 and GCV reduced both — added
  • muscle mass: no treatment effects on any muscle group (Table 2) — added to Key Results and Limitations
  • Cdkn1a effect size: ~46% amelioration of age-related increase; expression near-young levels
  • Ddit4 RT-PCR: significantly lower in Old Fisetin vs Old Veh (**p<0.01, Fig. 3F) — confirmed
  • Design section fully populated from Methods (previously placeholder)
  • Comparability claim nuance updated: authors themselves note possible greater effect of GCV/ABT-263 on p16+ clearance
  • Funding: updated to match paper disclosures exactly
  • ⚠️ banner removed; verified-date 2026-06-26; verified-by claude
• supersession check: no fisetin senolytic RCT or meta-analysis (aging/muscle/frailty endpoints) found post-2025; two 2026 obesity/inflammation RCTs and one 2022 PK RCT found — not superseding; literature-checked-through: 2026-06-26
• downstream propagation needed: fisetin compound page — the “no direct cell count in muscle” caveat should be added; senolytics if it cites Murray 2025