Ozarslan, Bengisu

BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert systemic metabolic and anti-inflammatory effects that may be relevant to cellular senescence, a key driver of skin aging. However, human cutaneous data are lacking. OBJECTIVE To explore whether systemic GLP-1RA therapy translates to a detectable reduction in cutaneous senescence, quantified by epidermal p21 expression and supported by AI-driven facial imaging. MATERIALS AND METHODS In this controlled observational pilot study, 3 male adults (GLP-1RA n = 2; GLP-1RA–naïve control n = 1) underwent 3-mm punch biopsies from a standardized, sun-protected gluteal site to isolate intrinsic aging. Senescence was quantified through blinded whole-epidermis digital annotation of p21-positive nuclei. Clinical phenotypes were assessed using noninvasive cheek measurements and AI-based facial age estimation. RESULTS The cohort demonstrated divergence in senescence-associated biomarkers correlating with GLP-1RA exposure. The GLP-1RA–naïve control exhibited 8.0% ( n = 2,062 nuclei) epidermal senescence. By contrast, participants with 163 and 62 days of GLP-1RA exposure showed reduced senescence burdens of 2.4% ( n = 2,045) and 0.6% ( n = 1,636), respectively. Automated facial age estimation remained concordant with chronological age across subjects. CONCLUSION Systemic GLP-1RA exposure is associated with a substantial reduction in epidermal p21 expression in some subjects, suggesting a senomorphic effect and supporting further mechanistic studies at the interface of metabolic regulation and skin aging.

ABSTRACT Background Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with substantial impairment in quality of life and psychological well‐being. The impact of cumulative treatment exposure and its relationship with multidimensional disease burden in HS has not been sufficiently discussed. The aim of this study is to investigate the associations between cumulative treatment burden, quality of life impairment, psychological symptom burden, disease activity, and patient‐perceived severity in patients with HS. Methods This multicenter cross‐sectional study included previously treated adult HS patients. Participants completed validated Turkish versions of the Dermatology Life Quality Index (DLQI), Symptom Checklist‐90‐Revised (SCL‐90‐R), and the Hidradenitis Suppurativa Self‐Assessment Tool (HSSA). A Treatment Burden Index (TBI) was developed to quantify cumulative therapeutic exposure based on guideline‐weighted treatment modalities. Results Ninety‐three patients were included (mean age 34.5 ± 11.0 years; 57% male). Higher TBI was moderately correlated with greater QoL impairment (Spearman ρ = 0.401, p < 0.001) and flare frequency. TBI was weakly correlated with psychological symptom burden. DLQI scores were positively associated with flare frequency and SCL‐90‐R scores, whereas the SCL‐90‐R scores were not associated with flare frequency or patient‐perceived disease severity. Conclusions HS burden is multidimensional, with partially independent domains of disease activity, treatment burden, quality of life impairment, and psychological distress. Cumulative treatment exposure is closely linked to QoL impairment and disease activity but only weakly associated with psychological symptom burden. Identification of distinct burden phenotypes may facilitate more personalized and patient‐centered management strategies in HS. image