Guo Xiaomei, Kassab Ghassan S
California Medical Innovations Institute, San Diego, CA, United States.
Front Physiol. 2020 Jun 9;11:591. doi: 10.3389/fphys.2020.00591. eCollection 2020.
The anti-aging function of Klotho gene has been implicated in age-related diseases. The physiological importance of Klotho in the progression of arterial stiffness with aging, however, remains unclear. The goal of this study is to determine the correlation of circulating Klotho with early age-related aortic stiffening and peripheral hemodynamics. We measured serum Klotho levels in a group of pigs with age ranges of 1.5-9 years and investigated the relationship between Klotho levels and biomarkers of aortic stiffening with aging, including aortic pulse wave velocity (PWV), augmentation index (AIx), and pulse pressure (PP). The effects of aortic stiffening on peripheral vascular resistance, compliance, and function were also evaluated. We found that increased aortic stiffness occurred at middle age (>5 years old), as evidenced by an increase in PWV and AIx ( < 0.001), but with no changes in blood pressure and PP. With advancing age, increased femoral vascular resistance positively correlated with aortic PWV and AIx ( < 0.01). No significant difference in endothelium function and arterial compliance for femoral and small peripheral arteries was observed between young and middle-aged groups. The serum Klotho levels were lower in young and higher in middle-aged pigs ( < 0.001), and a positive correlation was found between Klotho and aortic PWV, AIx, and femoral vascular resistance ( < 0.01). Our findings suggest that early-aged aortic stiffening has adverse effect on peripheral hemodynamics, independent of blood pressure levels. Elevated Klotho secretion was associated with increased aortic stiffness and peripheral vascular resistance with aging.
Klotho基因的抗衰老功能与年龄相关疾病有关。然而，Klotho在衰老过程中动脉僵硬度进展中的生理重要性仍不清楚。本研究的目的是确定循环中的Klotho与早期年龄相关的主动脉硬化和外周血流动力学之间的相关性。我们测量了一组年龄在1.5至9岁之间的猪的血清Klotho水平，并研究了Klotho水平与衰老相关的主动脉硬化生物标志物之间的关系，包括主动脉脉搏波速度（PWV）、增强指数（AIx）和脉压（PP）。还评估了主动脉硬化对外周血管阻力、顺应性和功能的影响。我们发现，中年（>5岁）时主动脉僵硬度增加，表现为PWV和AIx升高（<0.001），但血压和PP无变化。随着年龄的增长，股动脉血管阻力增加与主动脉PWV和AIx呈正相关（<0.01）。青年组和中年组之间，股动脉和外周小动脉的内皮功能和动脉顺应性无显著差异。青年猪的血清Klotho水平较低，中年猪的血清Klotho水平较高（<0.001），并且发现Klotho与主动脉PWV、AIx和股动脉血管阻力呈正相关（<0.01）。我们的研究结果表明，早期主动脉硬化对外周血流动力学有不利影响，与血压水平无关。随着衰老，Klotho分泌增加与主动脉僵硬度增加和外周血管阻力增加有关。
