Journal of Cachexia, Sarcopenia and Muscle (JCSM) - Abstract

 Volume 2, Number 1, Page 57 - 62


Sirtuin 1 in skeletal muscle of cachectic tumour-bearing rats: a role in impaired regeneration?

Míriam Toledo, Sílvia Busquets, Elisabet Ametller, Francisco J. López-Soriano, Josep M. Argilés

Background: 
In advanced malignant disease, cachexia and muscle wasting appear to be among the most common manifestations. This phenomenon is partially related with a decreased muscle regeneration capacity, as previously described in our laboratory.
Methods and results: 
Rats bearing the Yoshida AH-130 ascites hepatoma were used in the experiments. The animals experienced a marked weight loss with decreases in skeletal muscle weights (13% gastrocnemius, 18% extensor digitorum longus, and 12% tibialis muscles). Muscle gene expression was measured using real-time polymerase chain reaction. Skeletal muscle from cachectic tumour-bearing rats is associated with a decreased expression of genes involved in regeneration such as Pax-7 (39%), myogenin (24%), and MyoD (17%). mRNA levels of Sirt1 increased (91%) in cachectic skeletal muscle. The Sirt1 gene has been shown to be associated with changes in muscle myoblast differentiation. Treatment of the tumour-bearing animals with formoterol—a beta2-agonist—normalizes the expression of genes involved in regeneration (i.e., increase of Pax7 (139%)), at the same time as it does with that of Sirt1 (42% decrease).
Conclusions: 
It is suggested that the lack of muscle regeneration observed during muscle wasting in tumour-bearing animals is linked to the action of Sirt-1, possibly via PGC-1α. These factors may constitute possible targets of pharmacological treatment against muscle loss, thus potentially contributing to the understanding and mitigation of muscle atrophy associated with disease.

Toledo M, Busquets S, Ametller E, López-Soriano FJ, Argilés JM. Sirtuin 1 in skeletal muscle of cachectic tumour-bearing rats: a role in impaired regeneration? J Cachex Sarcopenia Muscle 2011;1:57-62.