PO:01:007 | Modulation of cellular senescence in psoriatic arthritis: exploring the potential impact of b/tsdmards treatment on telomere length, mtdna copy number, and oxidative damage
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background Inflammation and cellular senescence are interrelated processes involved in aging and chronic diseases. In Psoriatic Arthritis (PsA), excessive reactive oxygen species may contribute to telomere shortening and mitochondrial dysfunction. By reducing inflammation, biologic and targeted-synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs) could influence senescence pathways. This study aimed to evaluate biomarkers of cellular senescence in PsA patients receiving b/tsDMARDs, specifically telomere length (TL), mitochondrial DNA (mtDNA) copy number, and oxidative damage at therapy initiation (T0) and after 12 months (T12). Methods PsA patients starting b/tsDMARDs (TNF-alpha-i,IL17i, or JAKi) were enrolled and monitored over 12 months using DAPsA scores to classify them as Responders or non-Responders. Blood samples were collected at baseline (T0) and at 12 months (T12); age- and sex-matched healthy controls (CTRLs) were also included. TL and mtDNA copy number were measured in PBMCs using quantitative PCR. Oxidative DNA damage in telomeric and mitochondrial regions was assessed via qPCR after enzymatic digestion with FPG, measuring DeltaCt values. Statistical comparisons were performed using non-parametric or paired tests as appropriate, with significance set at p =< 0.05. ROC curves were used to assess discriminative potential of TL and mtDNA copy number. Results Our cohort included 50 PsA patients and 34 CTRLs, with a prevalence of female participants in both groups. PsA patients had a mean disease duration of 7.41 ± 6.43 years. (Table 1) PsA patients showed significantly shorter TL compared to CTRLs (median TL:0.025 vs. 0.050; p = 0.005). (Figure 1) TL positively correlated with disease duration (p = 0.042) and BMI (p = 0.011), and was higher in patients with metabolic comorbidities (p = 0.025). Telomeric oxidative damage showed no significant group difference but tended to increase in patients with longer disease duration and higher DAPsA. mtDNA copy number was significantly reduced in PsA patients versus CTRLs (median:16.43 vs. 26.71; p < 0.0001)(Figure 2) and correlated with BMI (p = 0.007). No significant difference in oxidative mtDNA damage was observed. ROC analysis showed that TL (AUC= 0.729) and mtDNA copy number (AUC= 0.760) discriminated PsA from CTRLs with moderate sensitivity and high specificity. A combined model yielded an AUC of 0.828 with 93.7% specificity. After 12 months of treatment, 36 patients were classified as Responders. In these, TL significantly increased compared to baseline (median TL at T12: 0.055; p = 0.0009), reaching values comparable to CTRLs. This effect was confirmed in subgroups treated with TNF-alpha-i (p = 0.04) and IL17i (p = 0.02).(Figure 3) mtDNA copy number did not significantly change post-treatment. Conclusions This study provides novel insights suggesting the potential use of TL and mtDNA copy number as biomarkers for assessing cellular senescence in PsA. b/tsDMARDs may have a modulatory effect on telomeric attrition and senescence pathways.
Source: Reumatismo
Author: PAGEPress Publications
Institution: PAGEPress (Italy)
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4415026892
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