Increased epigenetic age acceleration in the hidradenitis suppurativa skin.

Epigenetic (or DNA methylation) age is calculated based on methylation of certain cytosine-guanine (CpG) repeats, and it can accurately estimate one's chronologic age. Importantly, epigenetic age acceleration (EAA) is highly predictive of age-associated morbidity and all-cause mortality. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with significant systemic disease burden. Here, we performed a pilot study to calculate EAA from formalin-fixed paraffin-embedded skin samples using Illumina Infinium MethylationEpic BeadChip arrays. Our results demonstrated no significant difference in intrinsic EAA among HS compared to controls (- 1.00 years, p-value = 0.52), significant increases in both extrinsic EAA (13.72 years, p-value < 0.001) and PhenoAge acceleration (7.72 years, p-value = 0.003), and a significant decrease in GrimAge acceleration (- 5.14 years, p-value < 0.001). Our findings suggest that the acceleration of epigenetic age in the HS skin may be associated with extrinsic immune-related changes and can potentially serve as a biomarker of the present and/or future disease burden in HS patients.