Components of a skeletal muscle z-disc mechanosensor: do they contribute to the age related decline of muscle function in humans?

Overview

This project looks at the genetic elements of the molecular sensors that allow skeletal muscles to sense loads and respond and adapt accordingly. The project has been pivotal to setting up a new collaborative link with a research group at the University of Sao Paolo in Brazil.

In detail

Muscle wasting is a known morbidity factor in many clinical or behavioural conditions involving chronic muscle paralysis and there are no effective countermeasures to prevent it. This project aimed to start to identify the genetic elements of the molecular sensors which are involved in converting mechanical signals into biochemical ones and allowing skeletal muscles to sense loads. A secondary part of the project was to measure the activity of genes that participate in these mechanosensors in young and old muscles, both in humans and in mice. The intention being to test the hypothesis that one reason behind the inexorable decline of muscle power with age is that muscles become progressively less efficient at sensing and adapting to loads, because the mechanosensor complex changes over time.

The most significant finding was that over-expression of the z-disc protein KY in adult skeletal muscle increases the fibre diameter significantly. Thus, KY is sufficient to generate a hypertrophic response in the absence of overload stimulation. An oral presentation on the findings will be given at the 42nd European Muscle Conference.

The award has been pivotal to set up a new collaborative link with a group at the University of Sao Paolo led by Dr Elen Miyabara. Under this new collaboration, a large-scale project focusing on applying new experimental paradigms for characterizations of muscle phenotypes in the mouse has been submitted to the BBSRC-FAPESP scheme (FAPESP is a major Brazilian funding body).

Outputs

Grants

• Gonzalo Blanco, BBSRC, PhD studentship (Mechanistic Biology): 'Mechanistic role of KY in hypertrophy in mouse and fish', £93,471

Publications

• Can T., Faas L., Ashford David A., Dowle A., Thomas J., O'Toole P., and Blanco, G. (2014). Proteomic analysis of laser capture microscopy purified myotendinous junction regions from muscle sections. Proteome Science 2014, 12:25  doi:10.1186/1477-5956-12-25