αKlotho is a gene regulator of aging, increasing life expectancy when overexpressed and accelerating the development of aging phenotypes when inhibited. In mice, expression levels of the secreted isoform Klotho (s-KL) are very high in the brain, suggesting that s-KL activity may have an important role in the nervous system. Here we study the functional relevance at behavioural level of modifying s-KL levels in the aging brain. We used AAVrh10 vectors to deliver and sustained expression of s-KL in 6- and 12-month-old wild-type C57BL/6J males. This study demonstrates for we believe the first time in vivo that 6 months after a single injection of s-KL into the central nervous system, long-lasting and quantifiable enhancement of learning and memory capabilities are found. More importantly, cognitive improvement is also observable in 18-month-old mice treated once, at 12 months of age. These findings demonstrate the therapeutic potential of s-KL as a treatment for cognitive decline associated with aging.

中文翻译：

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分泌的αKlotho同工型可防止年龄依赖性记忆缺陷。

αKlotho是衰老的基因调节剂，在过度表达时可延长预期寿命，在被抑制时可加速衰老表型的发展。在小鼠中，大脑中分泌的亚型Klotho（s-KL）的表达水平很高，这表明s-KL活性可能在神经系统中起重要作用。在这里，我们研究了行为水平上的功能相关性，该行为水平是在衰老的大脑中修改s-KL水平的。我们使用AAVrh10载体在6个月和12个月大的野生型C57BL / 6J男性中传递和持续表达s-KL。这项研究表明，我们相信，单次将s-KL注射入中枢神经系统6个月后，首次发现了体内持久且可量化的学习和记忆能力增强。更重要的是，在12个月大时接受一次治疗的18个月大小鼠中，也可以观察到认知能力的改善。这些发现证明了s-KL作为与衰老相关的认知下降的治疗方法的治疗潜力。