The proBNPage Reduction (PBAR) Randomized Trial: a Pilot Study to Define the Characteristics of Future Randomized Trials Aimed at Evaluating the Effects of Anti-aging Treatments on a Surrogate of Biological Age in Healthy Older Adults

Background - The research on the possibilities to extend longevity in humans is presently based on large and long randomized longitudinal studies designed to compare all-cause mortality between treated and control groups. The availability of a simple and reliable marker of biological age might allow an acceleration of the research in this field, demonstrating in small samples and after limited periods of time, the ability of a given treatment to slow down, arrest or even revert the progression of biological age. Our previous studies suggest that this marker of biological age might be the N-terminal of B-type natriuretic peptide precursor (NT-proBNP), from which proBNPage, namely a biological age surrogate in years, can easily be calculated. Objectives of the study - 1) To fine-tune the method of proBNPage assessment, i.e., to establish the minimum time required to detect a significant increase in proBNPage in a small group of subjects. This will be the duration of next studies to test possible "anti-age" treatments. 2) To assess the ability of 4 "anti-age" treatments, which provided promising results in previous experimental and human studies, to modify proBNPage progression. Study design - Double-blind randomized clinical trial on a sample of healthy older adults stratified for age and sex. Study description - One hundred and twenty healthy subjects (in particular, without previous or current cardiovascular diseases) aged 65-80 years of both sexes will be randomized into 3 groups: A) Coenzyme Q10 100 mg bid + Selenium 100 mcg; B) Resveratrol 350 mg bid + TA-65 MD 100 U; C) Placebo-1 bid + Placebo-2. All these subjects will be followed for 2 years and checked 8 times, to assess both proBNPage progression and the safety of the treatments. Handgrip strength, aerobic capacity at the step test and quality of life will also be assessed. Statistical analysis - In the placebo group, the minimum time required to obtain a significant increase in proBNPage will be established by paired t tests. In the treated groups, possible differences in proBNPage progression with the curve obtained in the placebo group will be sought, both according to intention to treat and in the subjects that will complete the study, by repeated measures ANOVA.