早老素PS1/PS2双敲除小鼠中klotho表达的下降和血磷的升高(英文)

为了探讨抗衰老基因klotho是否参与早老素presenilin 1/presenilin 2条件性双敲除(PS cDKO)小鼠的衰老症状,分析了PS cDKO小鼠中肾脏和大脑中klotho的表达.结果发现,与同龄正常对照小鼠相比,12月龄雌性PS cDKO小鼠中肾脏klotho表达明显下降,血磷水平明显升高,而血钙略微下调,但同时几乎没有观察到肾功能障碍;而在大脑中,早在3月龄时klotho水平就已发生下降.这些结果说明klotho可能与PScDKO小鼠的症状有关,其表达水平的下降可能导致了血磷浓度的上升,但不足以引发肾功能障碍.此外,klotho作为一个抗氧化和抗炎症的因子,其表达下降可能与PScDKO小鼠体内氧化压力和炎症反应的升高有关.

Decreased klotho expression and elevated blood phosphate level in presenilin PS1/PS2 conditional double knockout mice

In this study, we investigated the expression of klotho, an anti-aging gene, and its involvement of premature aging phenotypes of presenilin 1/presenilin 2 conditional double knockout (PS cDKO) mice. The results showed that renal klotho level was significantly decreased in 12-month-old female PS cDKO mice when compared with control mice. Meanwhile, significant elevations of plasma phosphorus but slight reduction of calcium and almost no sign of renal dysfunction were observed. In PS cDKO brains, down-regulated klotho level was observed as early as 3 months of age. These findings indicate a possible role of klotho in the disorders of PS cDKO mice. The declined klotho expression may be responsible for the excess blood phosphate, but it seems that such a moderate decline in klotho level and impaired phosphate metabolism were not sufficient to elicit renal dysfunction in PS cDKO mice. However, as klotho is an anti-oxidative and anti-inflammation factor, klotho decline may contribute to the increased oxidative stress and inflammation in PS cDKO mice.