Increased epigenetic age acceleration in hidradenitis suppurativa

DNA methylation is an epigenetic modification that regulates gene expression without altering the DNA sequence. It commonly occurs at cytosine-guanine (CpG) repeats on chromosomes under the influence of genetic and environmental factors. Studies have demonstrated that epigenetic age, as calculated based on methylation of certain CpG sites, can accurately estimate chronologic age. Moreover, epigenetic age acceleration (EAA) is highly predictive of age-associated disease burden and mortality risk. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with significant systemic disease burden. To date, EAA has not been evaluated in HS. In this study, we calculated four measures of EAA from formalin-fixed paraffin-embedded skin samples (11 control and 11 HS) using Illumina 850 methylation BeadChip arrays: intrinsic EAA (IEAA), extrinsic EAA (EEAA), PhenoAge acceleration (PhenoAA), and GrimAge acceleration (GrimAA). Our results demonstrated no significant difference in IEAA among HS compared to control patients (-1.00 years; permutation p value 0.52), significant increases in both EEAA (13.72 years; p value < 0.001) and PhenoAA (7.72 years; p value 0.003), and significant decrease in GrimAA (-5.14 years; p value < 0.001). Our findings suggest that the acceleration of epigenetic age in HS is driven by extrinsic factors, such as changes in the inflammatory and immune cell infiltrates in the skin, rather than non-immune intrinsic pathways of aging. Moreover, PhenoAA indicates an increased all-cause mortality risk in HS. The negative association of GrimAA with HS may be due to the average chronologic age of HS specimens at the time of the collection being significantly younger than those of controls. Future studies should be directed at understanding if appropriate interventions can halt and/or reverse EAA, which can potentially become a powerful biomarker in the management of HS.