Modulation of cellular senescence in psoriatic arthritis: exploring the potential impact of bDMARDs on telomere length, mtDNA copy number, and oxidative damage.

Inflammation and cellular senescence are two interconnected biological processes critical for several chronic diseases. Pro-inflammatory factors promote the accumulation of reactive oxygen species, which synergistically accelerate the deterioration process. This creates a feedback loop that exacerbates telomere attrition and mitochondrial dysfunction, hallmarks of cellular senescence. Conventional therapies have been shown to influence oxidative stress and consequently cellular senescence, while the impact of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) is poorly investigated. Our aim was to explore biomarkers of cellular senescence in a population of psoriatic arthritis (PsA) patients treated with different b/tsDMARDs; we evaluated telomere length (TL), mtDNA copy numbers and oxidative damage at the beginning of therapy and after 12 months. We enrolled 50 PsA patients starting a b/tsDMARDs treatment and monitored the response to treatment for 12 months, based on the Disease Activity Index for PsA score, to identify subgroups of patients: responders and non-responders. We collected a blood sample for each patient at the beginning of therapy and after 12 months. In addition, we collected blood samples of 34 age- and sex-matched controls (CTRLs). We evaluated the cellular senescence biomarkers by qPCR. PsA patients at T0 showed a lower TL and fewer mtDNA copy numbers with respect to CTRLs (P < 0.001). Moreover, oxidative telomeric and mitochondrial damage seems to correlate positively with BMI (P < 0.05). We performed a combined ROC curve analysis to evaluate their ability to discriminate the two groups, showing an AUC of 0.828 with 59.2% sensitivity and 93.7% specificity. After 12 months of treatment monitoring, we classified 36 patients as responder and observed a TL significantly longer compared to T0 (P < 0.001), reaching comparable values to those of the CTRLs group. After patients' stratification based on the class of drugs, the result is confirmed in patients treated with TNFαi and IL17Ai. Our study provides novel insights for the molecular mechanism underlying PsA pathogenesis, highlighting the potential use of TL and mtDNA copy numbers as biomarkers for assessing cellular senescence in PsA. Moreover, our results also suggested that b/tsDMARDs may decelerate cellular senescence in PsA by preserving telomere length.