Leibniz-Institute on Aging - Fritz-Lipmann-Institute, Beutenbergstrasse 11, 07745, Jena, Germany.
Present address: Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125, Berlin, Germany.
Skelet Muscle. 2018 Jul 4;8(1):20. doi: 10.1186/s13395-018-0166-x.
Klotho is a well-known anti-aging hormone, which serves as a suppressor of aging through a variety of mechanisms. Aging of skeletal muscle is concomitant with a decrease in muscle stem cell function resulting in impaired regeneration.
Here we investigate the functional role of the anti-aging hormone Klotho for muscle stem cell function after cardiotoxin-induced injury of skeletal muscle using a klotho hypomorphic mouse line, which is characterized by a premature aging phenotype. Furthermore, we perform floating single myofiber cultures with their adjacent muscle stem cells to investigate the interplay between canonical Wnt signaling and Klotho function.
We demonstrate that muscle stem cell numbers are significantly decreased in klotho hypomorphic mice. Furthermore, we show that muscle stem cell function is also severely impaired upon loss of klotho expression, in culture and during regeneration in vivo. Moreover, we demonstrate that addition of recombinant Klotho protein inhibits aberrant excessive Wnt signaling in aged muscle stem cells thereby restoring their functionality.
The anti-aging hormone Klotho counteracts aberrant canonical Wnt signaling in muscle stem cells and might be one of the naturally occurring inhibitors of canonical Wnt signaling in skeletal muscle.
Klotho 是一种众所周知的抗衰老激素，通过多种机制抑制衰老。骨骼肌衰老伴随着肌肉干细胞功能的下降，导致再生受损。
在这里，我们使用 klotho 功能减弱的小鼠系研究抗衰老激素 Klotho 在心脏毒素诱导的骨骼肌损伤后对肌肉干细胞功能的作用，该小鼠系表现出早衰表型。此外，我们进行漂浮的单个肌纤维培养及其相邻的肌肉干细胞，以研究经典 Wnt 信号和 Klotho 功能之间的相互作用。
我们证明 klotho 功能减弱的小鼠中肌肉干细胞数量明显减少。此外，我们还表明，在体外培养和体内再生过程中，klotho 表达缺失也严重损害了肌肉干细胞功能。此外，我们证明添加重组 Klotho 蛋白可抑制衰老肌肉干细胞中异常的过度 Wnt 信号，从而恢复其功能。
抗衰老激素 Klotho 可拮抗肌肉干细胞中异常的经典 Wnt 信号，可能是骨骼肌肉中经典 Wnt 信号的天然抑制剂之一。
