Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle
Abstract 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 ro...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-07-01
|
| Series: | Skeletal Muscle |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13395-018-0166-x |
| _version_ | 1811197404442001408 |
|---|---|
| author | Hellen E. Ahrens Judith Huettemeister Manuel Schmidt Christoph Kaether Julia von Maltzahn |
| author_facet | Hellen E. Ahrens Judith Huettemeister Manuel Schmidt Christoph Kaether Julia von Maltzahn |
| author_sort | Hellen E. Ahrens |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T01:14:14Z |
| format | Article |
| id | doaj.art-424f0ac274564f9186109785fe5582d2 |
| institution | Directory Open Access Journal |
| issn | 2044-5040 |
| language | English |
| last_indexed | 2024-04-12T01:14:14Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Skeletal Muscle |
| spelling | doaj.art-424f0ac274564f9186109785fe5582d22022-12-22T03:54:01ZengBMCSkeletal Muscle2044-50402018-07-018111410.1186/s13395-018-0166-xKlotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscleHellen E. Ahrens0Judith Huettemeister1Manuel Schmidt2Christoph Kaether3Julia von Maltzahn4Leibniz-Institute on Aging – Fritz-Lipmann-InstituteLeibniz-Institute on Aging – Fritz-Lipmann-InstituteLeibniz-Institute on Aging – Fritz-Lipmann-InstituteLeibniz-Institute on Aging – Fritz-Lipmann-InstituteLeibniz-Institute on Aging – Fritz-Lipmann-InstituteAbstract 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.http://link.springer.com/article/10.1186/s13395-018-0166-xSkeletal muscleRegenerationKlothoMyogenesisMuscle stem cellAging |
| spellingShingle | Hellen E. Ahrens Judith Huettemeister Manuel Schmidt Christoph Kaether Julia von Maltzahn Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle Skeletal Muscle Skeletal muscle Regeneration Klotho Myogenesis Muscle stem cell Aging |
| title | Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle |
| title_full | Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle |
| title_fullStr | Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle |
| title_full_unstemmed | Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle |
| title_short | Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle |
| title_sort | klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle |
| topic | Skeletal muscle Regeneration Klotho Myogenesis Muscle stem cell Aging |
| url | http://link.springer.com/article/10.1186/s13395-018-0166-x |
| work_keys_str_mv | AT helleneahrens klothoexpressionisaprerequisiteforpropermusclestemcellfunctionandregenerationofskeletalmuscle AT judithhuettemeister klothoexpressionisaprerequisiteforpropermusclestemcellfunctionandregenerationofskeletalmuscle AT manuelschmidt klothoexpressionisaprerequisiteforpropermusclestemcellfunctionandregenerationofskeletalmuscle AT christophkaether klothoexpressionisaprerequisiteforpropermusclestemcellfunctionandregenerationofskeletalmuscle AT juliavonmaltzahn klothoexpressionisaprerequisiteforpropermusclestemcellfunctionandregenerationofskeletalmuscle |