Epigenetic consequences of changes in 8-hydroxy-2'-deoxyguanosine levels and their modification by TUDCA in patients with systemic metabolic disorders

Abstract

Background: Systemic metabolic disorders (SMDs) are highly prevalent. Oxidative stress (OS) and epigenetic modifications are key drivers of SMD progression.
Aims: to investigate changes in 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in patients with systemic metabolic disorders and to assess whether tauroursodeoxycholic acid (TUDCA) may modulate these changes as a potential mechanism for influencing inflammageing-related processes.
Methods: 57 patients with stage 1 SMD (median age 54.1 years; 68% male) and 20 age- and sex-matched healthy controls were evaluated. Patients received TUDCA 250 mg three times daily for 3 months alongside standard therapy. 8-OHdG and epigenetic markers, namely 5-methylcytosine (5-mC), telomere length (TL) and SIRT1 were measured at baseline and after treatment.
Results: At baseline, patients showed higher 8-OHdG (p = 0.012), shorter TL (p = 0.007), and increased 5-mC (p = 0.005) compared to controls. Post-TUDCA, TL increased (p < 0.001). Baseline 8-OHdG levels were associated with ?-1 globulin and urea, whereas post-TUDCA 8-OHdG levels were predicted by gamma-glutamyl transpeptidase and tumor necrosis factor alpha (p < 0.05). Changes in 8-OHdG were independently predicted (p < 0.001) by baseline 8-OHdG and the albumin-to-globulin ratio. Patients were also stratified by 8-OHdG response to TUDCA, revealing that group with a post-treatment reduction in 8 OHdG has baseline higher OS (p = 0.001), while TL showed greater elongation in patients with higher baseline 8 OHdG (p = 0.047).
Conclusions: Patients with SMDs exhibit adverse OS and epigenetic profiles. TUDCA therapy effect epigenetic aging and modulates OS. In patients with high baseline 8-OHdG, prolonged TUDCA treatment (likely >=6-12 weeks) or pre-treatment with additional antioxidants may be required to reduce oxidative stress and optimize telomere elongation.