🧬 Aging Wiki

il-11-receptor-alpha-1

Properties1
aliasesIL11RA, IL-11Rα, IL-11 receptor alpha, interleukin-11 receptor subunit alpha, Il11ra1

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IL-11 receptor alpha

IL11RA is the ligand-binding alpha subunit of the il-11 receptor. Ligand-bound IL11RA recruits IL6ST/gp130 to form a signaling complex that activates canonical JAK/STAT and non-canonical ERK-centered branches. The human gene is IL11RA; Il11ra1 is the conventional mouse symbol used in the requested animal studies.

Identity

  • Canonical human protein: UniProt Q14626.
  • Gene identifiers: NCBI Gene 3590; HGNC 5967; Ensembl ENSG00000137070. The mouse ortholog is Il11ra1 (MGI:107426) 1.
  • Human loss of function: homozygous damaging IL11RA variants were identified in five families with craniosynostosis, maxillary hypoplasia, delayed tooth eruption and supernumerary teeth; the tested p.Arg296Trp receptor failed to support IL-11-induced STAT3 phosphorylation in transfected cells 2. In mice, craniosynostosis-like and trabecular-bone abnormalities were reported with receptor loss but not in the compared Il11 ligand-null line 3.

Aging relevance

Old Il11ra1 knockout mice showed broad protection from age-associated metabolic, fibrotic and molecular changes, while aged Il11ra1 knockout ovaries were less stiff and fibrotic, had more secondary and fewer atretic follicles, and showed only a borderline increase in total healthy follicles (P=0.0503) versus wild-type controls 45. These germline models establish pathway involvement but are developmentally confounded.

In the ovarian study, primary human ovarian fibroblasts expressed IL11RA, and local AAV-mediated shRNA against mouse Il11ra1 reduced ovarian fibrosis and improved selected follicle and litter outcomes. The article did not report the AAV serotype, construct/promoter, shRNA sequence, genome dose/titer, injection volume, vendor, control-vector identity or biodistribution. No IL11RA-directed intervention has been tested for ovarian aging in women 5.

Pharmacology

LASN01 is a fully human anti-IL11RA antibody that completed a phase 1/2a study in healthy volunteers and people with pulmonary fibrosis or thyroid eye disease (n=75) and a phase 2 thyroid-eye-disease study (n=41). These non-aging programs establish human exposure and a preliminary safety dataset, not geroprotective efficacy, antifibrotic efficacy across organs or reproductive safety 6. Open Targets also maps approved oprelvekin to IL11RA as an agonistic cytokine ligand; that is not evidence for clinical receptor blockade in aging. Aging-context druggability is therefore tier 2 7. See anti-il-11-antibodies.

Key uncertainties

  • Whether IL11RA expression identifies the cell populations necessary for systemic aging effects remains unresolved.
  • Physiological relevance of IL-11 soluble-receptor trans-signaling and trans-presentation remains unresolved; the verified aging studies primarily test classic IL11RA-dependent signaling.
  • Constitutive receptor deletion cannot establish the safety of sustained adult antibody blockade. gap/long-term-unknown gap/needs-human-replication
  • Human GTEx age correlations and aging-directed Mendelian-randomization evidence remain unestablished. gap/needs-gtex-aging-correlation

Footnotes

Footnotes

  1. UniProt Q14626; NCBI Gene 3590; HGNC:5967; Ensembl ENSG00000137070; MGI:107426 · canonical database records accessed 2026-08-09 ↩

  2. doi:10.1016/j.ajhg.2011.05.024 · Nieminen P et al. · American Journal of Human Genetics 2011;89:67–81 · five families plus receptor-transfection and mouse experiments · primary human genotype–phenotype evidence ↩

  3. ng-2021-il11-il11ra1-loss-of-function · doi:10.1038/s41598-021-93623-9 · Ng B et al. · Scientific Reports 2021;11:14088 · ligand-versus-receptor loss-of-function, reproductive and craniofacial phenotypes ↩

  4. widjaja-2024-il11-healthspan-lifespan · doi:10.1038/s41586-024-07701-9 · mouse genetic and anti-IL-11 experiments ↩

  5. wu-2026-il11-ovarian-stiffness · doi:10.1038/s43587-026-01159-2 · human ovarian observations, cultured ovarian fibroblasts and rodent genetic/RNA interventions ↩ ↩2

  6. ClinicalTrials.gov NCT05331300 (phase 1/2a, n=75, completed 2024) and NCT06226545 (phase 2, n=41, completed 2025; results posted 2026) · registry records accessed 2026-08-09 ↩

  7. Open Targets Platform IL11RA record ENSG00000137070 · accessed 2026-08-09 · raw other-clinical precedence reflects oprelvekin; wiki tier is aging-context specific ↩

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