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

Author:

Opstad Trine Baur12,Alexander Jan3ORCID,Aaseth Jan45ORCID,Larsson Anders6ORCID,Seljeflot Ingebjørg12ORCID,Alehagen Urban7

Affiliation:

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.

Funder

Stein Erik Hagen Foundation for Clinical Heart Research, Oslo, Norway

Pharma Nord Aps, Vejle, Denmark

County Council of Östergötland, Linköping University, Sweden

Publisher

MDPI AG

Subject

Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology

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