Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Ahrens|Hellen E|HE|', 'Huettemeister|Judith|J|', 'Schmidt|Manuel|M|', 'Kaether|Christoph|C|', 'von Maltzahn|Julia|J|0000-0001-7674-1487']
D000375:Aging D019588:Aging, Premature D000818:Animals D002454:Cell Differentiation D049109:Cell Proliferation D002478:Cells, Cultured D005966:Glucuronidase D000090265:Klotho Proteins D008810:Mice, Inbred C57BL D008817:Mice, Mutant Strains D024510:Muscle Development D018482:Muscle, Skeletal D032448:Myoblasts, Skeletal D012333:RNA, Messenger D012038:Regeneration D060449:Wnt Signaling Pathway D060509:Wnt3A Protein
Klotho Muscle stem cell Regeneration Skeletal muscle Aging Canonical Wnt signaling, Wnt3a Myogenesis