R27

log/R27.md — Round 27 entries

Sub-file of log — see parent for index.

[2026-05-07] R27 propagation pass

Propagation for the R27 batch (5 newly-verified pages: studies/waziry-2023-calerie-epigenetic-clock, processes/unfolded-protein-response, molecules/proteins/hsp90, pathways/il-1-signaling, molecules/compounds/anakinra).

• updated: hallmarks/loss-of-proteostasis.md (added hsp90 wikilink + sibling note in chaperones section; added new “Unfolded protein response — the ER-stress arm” subsection cross-linking unfolded-protein-response alongside the existing ISR section; added unfolded-protein-response, hsp90, hsp70 to Cross-references list)
• updated: hallmarks/chronic-inflammation.md (added il-1-signaling integration note in NLRP3 inflammasome section; expanded therapeutic-landscape “Anti-IL-1β” subsection → “Anti-IL-1 axis” covering both canakinumab and anakinra; documented Salmon 2022 IL-1α/AAA paradox as a worked translation-tension example with new [^salmon2022] footnote; added cross-links in Interventions section)
• no edit needed: hypotheses/information-theory-of-aging.md (already wikilinks [[studies/waziry-2023-calerie-epigenetic-clock]] in key-evidence-against: frontmatter, body discussion sections, and [^waziry2023] footnote; quantitative claims already match verified study)
• updated: pathways/heat-shock-response.md (druggability-tier 1 → 2 per R26 schema clarification — heat-shock-response is the explicit worked example in CLAUDE.md; rewrote oncology-context discussion to remove tier-1 framing; replaced schema-ambiguity Limitations bullet with resolution note)
• no edit needed: interventions/lifestyle/caloric-restriction.md (already wikilinks [[studies/waziry-2023-calerie-epigenetic-clock]] in body and footnote; already documents PhenoAge/GrimAge null + DunedinPACE d=−0.25 + ~12% CR achieved)
• no edit needed: molecules/compounds/canakinumab.md (fatal-infection wording already uses correct incidence rate format “0.31 vs 0.18 events per 100 person-years (P=0.02)” — NOT the incorrect HR ~1.7 phrasing; anakinra already cross-linked in Target Specificity and Cross-references)
• updated: molecules/proteins/il-1r1.md (refreshed “implicit stub” annotations on il-1-signaling cross-link; added R27-resolved note to Limitations)
• updated: molecules/proteins/il-1ra.md (refreshed “Implicit stubs from this page” block — il-1-signaling and anakinra now seeded/verified)
• updated: molecules/proteins/il-1b.md (added il-1-signaling to Pathway membership cross-references; updated Family-completion cross-links block to mark il-1-signaling + anakinra as R27-seeded)
• no edit needed: molecules/proteins/il-1a.md, molecules/proteins/il-18.md (both already have il-1-signaling wikilinks in pathways frontmatter and cross-references sections)
• updated: molecules/proteins/hsp70.md (resolved “unfolded-protein-response when that page exists” stub annotation → now wikilinks verified UPR page; added new sibling-chaperone-family paragraph cross-linking hsp90 with cooperative-mechanism context and druggability-tier split)
• updated: biomarkers/dunedinpace-2022.md, biomarkers/phenoage-2018.md (refreshed “primary CALERIE-2 clock study page (stub)” annotations → “(verified R27)”)
• no edit needed: biomarkers/grimage-2019.md (already wikilinks waziry-2023 in cross-references and footnote; no stub annotation present)

Naming-convention findings:

• IL-1α file is il-1a.md (not il-1alpha.md as the propagation brief listed) — alias il-1alpha is in the file’s aliases: frontmatter for ambiguous-link resolution.
• HSC70 file path resolved cleanly (hsc70.md is the canonical CMA-context cytosolic HSP70 paralog page; HSPA8/HSC73 covered there).

Schema/lint observations surfaced this pass:

• The previously-flagged “druggability-tier semantic ambiguity for pathway pages” Limitations bullet on heat-shock-response.md is now closed by R26 schema clarification + this propagation pass — both heat-shock-response (pathway, tier 1→2) and hsp90 (protein, tier 1→2 per R27 verifier) now consistent.
• The IL-1 family page-cluster (il-1-signaling pathway + il-1a/b/r1/ra/18 proteins + canakinumab/anakinra compounds + nlrp3-inflammasome upstream + caspase-1/asc/gsdmd/pyroptosis processing) is now schematically complete with the R27 additions; il-1b.md cross-references block updated to reflect this.
• No reverse personal → research wikilinks introduced this pass; one-way discipline preserved.