Human Muscle Gene Expression Profiles in Young and Old Men

To reach the goals of living longer in better medical conditions, many countries reach the same conclusion: new strategies have to be developed to avoid, or at least limit, the effects of age; this requires a better knowledge of the mechanisms of aging. Our project focuses on the loss of muscle mass associated with aging, called sarcopenia. Sarcopenia unavoidably leads to impaired mobility and poor balance, which contributes to loss of functional autonomy and to increased prevalence for severe falls. Skeletal muscle also plays a central role as a reserve for energy and amino acids. Hence, sarcopenia further triggers severe side metabolic effects such as frailty among elderly persons. The precise mechanisms of muscle aging are still mostly unknown, although many theories have been proposed.

The present study aims at better understanding the mechanisms of skeletal muscle loss associated with aging. Using muscle biopsies from young and old subjects, the differential expression profiles of mRNA will be obtained through chips that will evaluate more than 39000 transcripts. On the same samples, proteomic analyses will involve two complementary approaches: (1) bidimensional electrophoresis (2DGE) coupled to mass spectrometry (MALDI-ToF) for dominant proteins; (2) Western-blot (more than 800 antibodies) targeting regulating proteins not detectable using 2DGE. Complementary histological studies (immunohisto-fluorescence, confocal microscopy) will specify the localisation of the major biomarkers in the muscle biopsies.

The results of that research will have applications in the medium term and will lead to nutritional interventions to modulate specific metabolic pathways and improve the quality of life in the elderly.