🧬 Aging Wiki

stat3

Properties1
aliasesSTAT3, signal transducer and activator of transcription 3, APRF, acute-phase response factor

2 min read

STAT3

STAT3 is a cytokine- and growth-factor-responsive transcription factor. Receptor-associated kinases phosphorylate STAT3 at Tyr705, promoting dimerization, nuclear entry and context-specific transcription. The canonical human identifiers are UniProt P40763, NCBI Gene 6774, HGNC 11364 and Ensembl ENSG00000168610; the mouse ortholog is Stat3 (MGI:103038) 1.

IL-11 context

The il-11–IL11RA–gp130 complex activates canonical STAT3/STAT1 signaling through gp130-associated JAK1, JAK2 and TYK2 2. The fibrosis and aging papers also emphasize a non-canonical ERK-centered branch. IL-11 activated both STAT3 and ERK in primary human lung fibroblasts, and both branches changed with IL-11 perturbation in aging mouse tissues, but the studies did not establish that STAT3 alone mediated healthspan, lifespan or ovarian-stiffness phenotypes 345.

This distinction matters because gp130-family cytokines converge on STAT3. Phospho-STAT3 is evidence of pathway activation, not a ligand-specific biomarker of IL-11, and broad STAT3 inhibition would affect immune, repair and metabolic signaling well beyond the IL-11 axis.

Aging interpretation and druggability

Open Targets records high-quality small-molecule ligands and a phase 2 antisense clinical candidate (danvatirsen) for STAT3, but the clinical program is not an aging intervention. Aging-context druggability is therefore tier 2: chemical and oligonucleotide probes exist, but no clinical drug has demonstrated an aging indication through selective STAT3 modulation 6. Ligand- or receptor-selective approaches such as anti-il-11-antibodies provide a narrower way to test one upstream cytokine axis.

Gaps

  • Cell-type-specific STAT3 necessity has not been separated from ERK and other branches in the IL-11 aging studies.
  • Total expression, Tyr705 phosphorylation, Ser727 phosphorylation and mitochondrial/non-transcriptional STAT3 functions should not be treated as interchangeable readouts.
  • Chronic systemic inhibition in older adults would require immune, infection, wound-healing and metabolic safety testing. gap/no-mechanism 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 P40763; NCBI Gene 6774; HGNC:11364; Ensembl ENSG00000168610; MGI:103038 · canonical database records accessed 2026-08-09 ↩

  2. Reactome R-HSA-449976 and R-HSA-6783589; WikiPathways WP2332 · human curated pathway records accessed 2026-08-09 ↩

  3. doi:10.3389/fimmu.2024.1293883 · Tan Y et al. · Frontiers in Immunology 2024;15:1293883 · primary human lung fibroblast and epithelial-cell signaling experiments · IL-11 activated both STAT3 and ERK ↩

  4. widjaja-2024-il11-healthspan-lifespan · doi:10.1038/s41586-024-07701-9 · Widjaja AA et al. · Nature 2024;632:157–165 ↩

  5. wu-2026-il11-ovarian-stiffness · doi:10.1038/s43587-026-01159-2 · Wu M et al. · Nature Aging 2026;6:1395–1416 ↩

  6. Open Targets Platform STAT3 record ENSG00000168610 · accessed 2026-08-09 · high-quality-ligand signal and danvatirsen phase 2 clinical-candidate row ↩

Graph View

Backlinks