Abstract 12293: RNAi Knockdown of Klotho Gene Causes Hypertension and Kidney Damage

Background & Hypothesis: Klotho is a recently-discovered anti-aging gene. Genetic mutation of klotho results in multiple premature aging phenotypes and significantly shortens lifespan. In contrast, overexpression of klotho extends lifespan. Thus, klotho may be an aging-suppressor gene that can delay aging when overexpressed and accelerate aging when disrupted. In humans, the level of the circulating klotho declines with age while the prevalence of hypertension increases with age. The objective of this study was to assess our hypothesis that knockdown of klotho leads to hypertension and kidney damage in rats. Methods and Results: The in vivo RNAi knockdown of klotho was achieved by AAV delivery of klotho shRNA (KLshRNA). In vivo expression of anti-inflammatory cytokine IL-10 was achieved by AAV delivery of human IL-10 full-length cDNA (IL10). RNAi knockdown of klotho significantly increased systolic and diastolic blood pressure. The KLshRNA-induced hypertension may be mediated by inflammation because it ca...