Fluid biomarkers of early vascular aging as the therapeutic targets

National Institute On Aging

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Abstract

The following experiment was performed to test the study hypotheses: Six-month old DSS female rats were treated with placebo (control group, n=11), or QRC (100 mg/kg BW/day; n=13), or a combination of QRC+DAS (n=6) for 6 months. DAS (1mg/kgBW/day) was added for the final 2 months to the QRC+DAS group. Systolic BP (SBP), pulse wave velocity (PWV, an index of CAS), echocardiography, cognitive function (visuospatial attention test and cross maze), and anxiety-like behavior (open field and elevated plus maze) were evaluated following treatment or placebo. We demonstrated that at 12 months of age, neither QRC nor QRC+DAS treatments affected SBP or PWV compared to controls. However, the senolytic treatments improved heart function, which was associated with increased ejection fraction. QRC+DAS treatment reduced left ventricle relative wall thickness (LV-RWT) versus controls. Cognitive function did not differ significantly among treated and control groups. However, the rats in both treated groups (QRC and QRC+DAS) exhibited reduced anxiety-like behavior spending more time in the open arms. Correct attention test responses inversely correlated with LV-RWT (r = -0.813, P = 0.004) and positively with cardiac output (r = 0.760, P=0.02) in the QRC group; for QRC+DAS group we observed negative correlation with LV-RWT (r = -0.683, P = 0.021) and a positive correlation with ejection fraction (r = 0.577, P = 0.063), suggesting a link between cardiac structure and attentional performance. Based on the results of this study we have concluded, that chronic senolytic treatments with QRC or QRC+DAS protected heart function and reduced anxiety-like behavior in aged DSS females, although this treatment did not affect elevated blood pressure and CAS. The correlation between cardiac remodeling and attention test performance scores highlights a potential heart-brain interaction and an association between improved cardiac parameters and cognitive performance.