Deficiency of skeletal muscle Agrin contributes to the pathogenesis of age-related sarcopenia in mice.
Cell Death Dis
; 15(3): 201, 2024 Mar 09.
Article
em En
| MEDLINE
| ID: mdl-38461287
ABSTRACT
Sarcopenia, a progressive and prevalent neuromuscular disorder, is characterized by age-related muscle wasting and weakening. Despite its widespread occurrence, the molecular underpinnings of this disease remain poorly understood. Herein, we report that levels of Agrin, an extracellular matrix (ECM) protein critical for neuromuscular formation, were decreased with age in the skeletal muscles of mice. The conditional loss of Agrin in myogenic progenitors and satellite cells (SCs) (Pax7 Cre Agrin flox/flox) causes premature muscle aging, manifesting a distinct sarcopenic phenotype in mice. Conversely, the elevation of a miniaturized form of Agrin in skeletal muscle through adenovirus-mediated gene transfer induces enhanced muscle capacity in aged mice. Mechanistic investigations suggest that Agrin-mediated improvement in muscle function occurs through the stimulation of Yap signaling and the concurrent upregulation of dystroglycan expression. Collectively, our findings underscore the pivotal role of Agrin in the aging process of skeletal muscles and propose Agrin as a potential therapeutic target for addressing sarcopenia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Agrina
/
Sarcopenia
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article