Unmasking molecular pathways of sarcopenia and muscle dysfunction and their biomarkers

About the Project

Sarcopenia is a disease that affects individuals both as part of the normal ageing process and as a consequence of systemic disease. In both cases, sarcopenia is known to be associated with significant impairments in quality of life and physical function as well as mortality. Pharmacological interventions to prevent and treat sarcopenia have had only limited success, potentially due to the poor understanding of the driving mechanisms behind the disease and a lack of measures able to predict its onset and progression among wider at-risk populations.

This project will apply both established and novel laboratory methods on previously collected skeletal muscle tissue to identify plausible molecular and metabolic pathways associated with clinical evidence of sarcopenia and physical dysfunction. Simultaneously, a literature review will be conducted to identify and select blood-based disease markers utilising proteomic and epigenetic analysis. These markers will be selected by their potential ability to identify the presence and/or risk of sarcopenia as well as specific pathways associated with sarcopenia and identified in the earlier muscle tissue analysis. Finally, identified feasible blood-based disease markers will be applied across samples from our biobank collected from previously characterised patients to evaluate these as predictive and diagnostic markers of sarcopenia and muscle dysfunction with potential to guide current and future pharmacological interventions.

Techniques that will be undertaken during the project

Research methods:

• Literature narrative review and critical appraisal
• Statistical skills and data handling including coding in R (e.g. proteomic data analysis)

Wet lab:

• Untargeted proteomic analysis using LCMS including data interrogation
• Morphological analysis
• Muscle histological staining for satellite cells (location and abundance), fatty infiltration (including intrafebrile fat deposits), fibre typing and fibre size measurement.