Effectiveness of a Fermented Functional Food on Telomere Dynamics and miRNAs in Middle-Aged/Elderly Healthy Individuals: A 2-Year Randomized, Double-Blind, Controlled Clinical Trial

Background: A specific fermented papaya preparation (ORI-FPP (R)), has been well established with non clinical and clinical val-idation in modulating redox and immune systems as well as mitochondrial efficiency. In addition, recent data from the Italian NIH (National Institute of Health) have shown that this compound was able to increase telomeres length and telomerase activity in an aged mouse model.Objective: The purpose of the study was to test the clinical effect of ORI-FPP (R) in healthy middle-aged/elderly subjects in terms of telomere dynamics and aging-related miRNAs (micro ribonucleic acids), as compared to an antioxidant formulation.Materials: The study population comprised 107 healthy non smoker middle-aged/elderly subjects (58 women and 49 men, mean age 56.6 +/- 13.8 years, age range 44-74 years) free from medications and with a mean body mass index (BMI) of 24.7 +/- 2.6. Subjects were double-blinded and randomly allocated to 2 groups: (A) ORI-FPP (R) 4.5 g plus 1 cp of cellulose and (B) flavoured sugar 4.5 g plus 1 cp containing a mix of antioxidants. Leucocyte telomere length (TL), gene expression related to telomere maintenance genes (TERT (telomerase reverse transcriptase) and Wrap53) and telomerase activity (TRAP) were assessed by quantitative reverse transcriptase-polymerase chain reaction after both nutraceutical interventions. This was also associated with gene expression evaluation of: SOD (superoxide dismutase), CAT (catalase), GPx1 (glutathione peroxidase-1) and hOGG1 (human 8-oxoguanine DNA glycosylase 1) as well as miRNA-146a and miRNA-181a. Dietary and psychological (10-item Cohen Perceived Stress Scale) questionnaires were administered at the start and throughout the two-year study. Results: TL was unaffected by treatments but a significant TL increase was observed at the end of the study in the 60-74 years old group treated with FPP (R). Gene expression of TERT and WRAP53 showed a significant upregulation (168% and 57%, re-spectively) in group A as compared with group B starting from the 6th month observation (p < 0.01 vs group B), together with TRAP (p < 0.05 vs group B). CAT, SOD1 and GPx1 were comparably upregulated by both treatments. However, only FPP (R) upregulated hOGG1, miRNA-146a and miRNA-181a. TERT and WRAP53 gene expressions were significantly correlated to GPx, hOGG1, miRNA-146a and miRNA-181a gene expression.Conclusions: These data suggest that ORI-FPP (R), unlike the antioxidant control formulation, could significantly benefit TL dy-namics. This phenomenon seemed correlated to a concomitant antioxidant and, namely, DNA (deoxyribonucleic acid)-protecting genes upregulation and aging-related miRNAs.