Proteomic and bioinformatic profiling of the aging mouse heart-diaphragm system

With advancing age, cardiac weakness and a progressive loss of skeletal muscle mass and contractile strength, is observed in most humans. Although considerable inter-individual differences exist in the degree of age-related muscle wasting, progressive cardiac impairment and sarcopenia play a key role during the natural aging process and form an integral part of the frailty syndrome. Here, we have used comparative bottom-up proteomic profiling to study age-related changes in an established murine model of sarcopenia. The simultaneous assessment of heart and diaphragm muscle aging using peptide mass spectrometry showed that senescence is associated with myofiber degeneration, considerable changes in metabolic processes and increased extracellular matrix deposition. A striking reduction in two mitochondrial enzymes, NAD(P) transhydrogenase and hydroxymethylglutaryl-CoA synthase, was identified by proteomics in the senescent heart and diaphragm muscle, respectively. Bioinformatic analyses revealed abundance changes in distinct protein families and potential alterations in protein-protein interaction patterns. The altered protein profile of the heart-diaphragm system, as determined by comparative discovery proteomics, can be helpful to establish an improved biomarker signature for diagnostic, prognostic and therapeutic monitoring of muscle aging.