Increased SIRT1 Concentration Following Four Years of Selenium and Q₁₀ Intervention Associated with Reduced Cardiovascular Mortality at 10-Year Follow-Up-Sub-Study of a Previous Prospective Double-Blind Placebo-Controlled Randomized Clinical Trial

• Main Authors: Trine Baur Opstad (Author), Jan Alexander (Author), Jan Aaseth (Author), Anders Larsson (Author), Ingebjørg Seljeflot (Author), Urban Alehagen (Author)
• Format: Book
• Published: MDPI AG, 2023-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox12030759; 2076-3921
• Keywords: sirtuin1; selenium; coenzyme Q₁₀; intervention; cardiovascular mortality; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 12, Iss 3, p 759 (2023)

<i>Background</i>: Selenium and coenzyme Q₁₀ (SeQ₁₀) possess antioxidant and anti-inflammatory properties, potentially mediated via Sirtuin1 (SIRT1). We aimed to investigate the influence of a SeQ₁₀ intervention on SIRT1 concentration, with potential interactions with microRNAs. <i>Methods</i>: In this sub-study of a prospective double-blind placebo-controlled clinical trial, healthy subjects (mean age 76 years) were randomized to receive an active treatment (<i>n</i> = 165, combined 200 µg/day of Se and 200 mg/day of Q₁₀) or a placebo (<i>n</i> = 161). SIRT1 concentration and microRNAs were measured with ELISA and PCR, respectively. <i>Results</i>: After four years, SIRT1 concentration was increased in the active treatment group, with mean (SD) ng/mL of 469 (436) vs. 252 (162), <i>p</i> < 0.001, and decreased in the placebo group, 190 (186) vs. 269 (172), <i>p</i> = 0.002, and the differences between the groups were significant (<i>p</i> = 0.006, adjusted). Those who suffered CV death during a 10-year follow-up (<i>n</i> = 25 and <i>n</i> = 52 in the active treatment and placebo groups, respectively) had significantly lower baseline SIRT1 concentrations compared to the survivors (<i>p</i> < 0.001). MiR-130a-3p was significantly downregulated during the intervention and correlated inversely with SIRT1 at baseline (r = −0.466, <i>p</i> = 0.007). <i>Conclusion</i>: The increased SIRT1 concentration after the SeQ₁₀ intervention associated with reduced CV mortality, partly mediated via miR-1303a-3p, suggests that SIRT1 is an additional mediator of the intervention, preventing vascular ageing.