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

Trine Baur Opstad; Jan Alexander; Jan Aaseth; Anders Larsson; Ingebjørg Seljeflot; Urban Alehagen

doi:10.3390/antiox12030759

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

Antioxidants (Basel). 2023 Mar 21;12(3):759. doi: 10.3390/antiox12030759.

Authors

Trine Baur Opstad^{1

2}, Jan Alexander³, Jan Aaseth^{4

5}, Anders Larsson⁶, Ingebjørg Seljeflot^{1

2}, Urban Alehagen⁷

Affiliations

¹ Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, P.O. Box 4950, Nydalen, N-0424 Oslo, Norway.
² Faculty of Medicine, University of Oslo, N-0370 Oslo, Norway.
³ Norwegian Institute of Public Health, P.O. Box 222, Skøyen, N-0213 Oslo, Norway.
⁴ Department of Research, Innlandet Hospital Trust, P.O. Box 104, N-2381 Brumunddal, Norway.
⁵ Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, N-2624 Lillehammer, Norway.
⁶ Department of Medical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden.
⁷ Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.

Abstract

Background: 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. Methods: 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 (n = 165, combined 200 µg/day of Se and 200 mg/day of Q₁₀) or a placebo (n = 161). SIRT1 concentration and microRNAs were measured with ELISA and PCR, respectively. Results: After four years, SIRT1 concentration was increased in the active treatment group, with mean (SD) ng/mL of 469 (436) vs. 252 (162), p < 0.001, and decreased in the placebo group, 190 (186) vs. 269 (172), p = 0.002, and the differences between the groups were significant (p = 0.006, adjusted). Those who suffered CV death during a 10-year follow-up (n = 25 and n = 52 in the active treatment and placebo groups, respectively) had significantly lower baseline SIRT1 concentrations compared to the survivors (p < 0.001). MiR-130a-3p was significantly downregulated during the intervention and correlated inversely with SIRT1 at baseline (r = -0.466, p = 0.007). Conclusion: 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.

Keywords: cardiovascular mortality; coenzyme Q10; intervention; selenium; sirtuin1.

Abstract

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