Association of SIRT1 with metabolic parameters and aging rate

Introduction: SIRT1 has attracted great interest due to its role as a regulator of longevity, and its therapeutic potential for the prevention and treatment of aging and age-related comorbidi-ties. However, the mechanisms by which SIRT1 influences the course of aging remain unknown. Methods: The study population included 88 apparently healthy subjects aged 31 - 65 without es-tablished atherosclerotic cardiovascular disease or metabolic-associated diseases. Clinical, anthro-pometric, and biochemical parameters were determined in all patients. Molecular genetic studies included the determination of the C/G polymorphism of the SIRT1 gene (SIRT1 , rs7069102), relative telomere length of blood leukocytes (RTL-b), and telomerase activity. Biological age was calculated using the DNAm PhenoAge epigenetic clock. Results: The SIRT1 serum levels in carriers of dif-ferent genotypes of the G/C polymorphism (rs7069102) and in patients of different age groups did not differ. SIRT1 plasma levels in the accelerated aging group were significantly higher in compar-ison with the healthy aging group: (4.16 +/- 1.18) ng/ml vs (3.47 +/- 0.76) ng/ml, respectively (p = 0.00066). Correlation analysis revealed a positive correlation of the SIRT1 serum level with uric acid (R = 0.25; p = 0.023), tissue necrosis factor (R = 0.26; p = 0.014), total hydroperoxides (R = 0.33; p = 0.003) and a negative correlation with low-density lipoprotein cholesterol (R =-0.22; p = 0.039), telomerase activity (R =-0.39; p = 0.001) and total antioxidant activity (R =-0.35; p = 0.001). Step-wise regression analysis revealed negative association of the SIRT1 serum level with biological age. Conclusion: SIRT1 plasma levels in apparently healthy subjects were associated with age, body mass index (BMI), WC, factors of carbohydrate metabolism, and markers of the pro-antioxidant bal-ance. A comparative analysis of SIRT1 plasma levels between accelerated and healthy aging groups showed a significant difference. However, our study did not confirm that SNPs (rs7069102) of the SIRT1 genotypes are associated with SIRT1 plasma level, aging rate, or any metabolic parameters.