Epigenetic Clock Acceleration in Spondyloarthritis Correlates With Cutaneous Dysbiosis and Seborrheic Keratosis Burden: A Longevity-Rheumatology Interface

Hypothesis: Spondyloarthritis (SpA) accelerates epigenetic aging via chronic IL-17/TNF-driven inflammation, which simultaneously promotes cutaneous dysbiosis (Malassezia overgrowth, HPV persistence) and seborrheic keratosis (SK) proliferation. SK burden may serve as a visible biomarker of biological aging acceleration in SpA patients.

Rationale:

1. SpA patients show elevated Horvath/GrimAge epigenetic clocks (preliminary data in RA/SLE, untested in SpA)
2. IL-17 axis — central to SpA — drives keratinocyte hyperproliferation via NF-kB/MAPK/PI3K-AKT
3. Cutaneous dysbiosis (gut-skin axis) is documented in psoriatic arthritis but unstudied in axial SpA
4. Malassezia association with SK documented since 1980 (6 studies)
5. ZERO publications linking SK with SpA — completely virgin territory
6. FinnGen summary statistics available for both phenotypes (L82 + M45) — Mendelian Randomization feasible

Proposed validation: FinnGen LDSC genetic correlation + bidirectional MR, followed by clinical pilot in Yucatan SpA cohort with SK burden quantification and skin microbiome sampling (16S/ITS2).

References: Chen et al. 2025 (PMID: 41262772), Visser et al. 2019 (PMID: 39624183), Bonomo 2025, Gracey 2019