Proteomic strategies to unravel age-related redox signalling defects in skeletal muscle

Abstract

Increased oxidative damage and disrupted redox signalling are consistently associated with age-related loss of skeletal muscle mass and function. Redox signalling can directly regulate biogenesis and degradation pathways and indirectly via activation of key transcription factors. Contracting skeletal muscle fibres endogenously generate free radicals (e.g. superoxide) and non-radical derivatives (e.g. hydrogen peroxide). Exercise induced redox signalling can promote beneficial adaptive responses that are disrupted by age-related redox changes. Identifying and quantifying the redox signalling pathways responsible for successful adaptation to exercise makes skeletal muscle an attractive physiological model for redox proteomic approaches. Site specific identification of the redox modification and quantification of site occupancy in the context of protein abundance remains a crucial concept for redox proteomics approaches. Notwithstanding, the technical limitations associated with skeletal muscle for proteomic analysis, we discuss current approaches for the identification and quantification of transient and stable redox modifications that have been employed to date in ageing research. We also discuss recent developments in proteomic approaches in skeletal muscle and potential implications and opportunities for investigating disrupted redox signalling in skeletal muscle ageing.