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24, chemin de Borde Rouge –Auzeville – CS52627
31326 Castanet Tolosan CEDEX - France

Dernière mise à jour : Mai 2018

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Human Nutrition Unit

Zone de texte éditable et éditée et rééditée

Daniel Béchet

Daniel Béchet's profile

Field of research

Aging affects most tissues and physiologic functions, but one of the most affected organs is the skeletal muscle. The age-related decline in muscle mass and function (sarcopenia) increases the risk of impaired mobility, poor balance, falls, and loss of autonomy. Skeletal muscle, which is the most abundant tissue in the adult body, also plays a central role as a reserve for energy and amino acids, and is a major site of fatty acid oxidation, carbohydrate metabolism and maintenance of heat homeostasis. Hence, age-related loss of muscle mass also triggers severe metabolic side effects, including metabolic syndrome and frailty in the elderly. Independently of other risk factors or disease, low skeletal muscle mass or strength is now reported to be a predictor of morbidity and mortality. A clear understanding of the mechanisms of sarcopenia through the identification of selective biomarkers is thus of paramount importance in ensuring quality of life in the old age.

To provide an integrative view of sarcopenia in human, we have undertaken top-down differential proteomic approaches, and we combined proteomics, transcriptomics, immunohistology and mass spectrometry molecular imaging to study unique cohorts of elderly subjects, and several sub-cohorts with age-related pathologies (hypertension, metabolic syndrome, etc.). Our studies provide major information about fiber type, morphology, oxidative metabolism, lipid droplets, apoptosis, capillarization, satellite cells and fibrosis of the extracellular matrix, together with mass spectrometry molecular imaging, and state of the art transcriptomic and 2D and shot-gun proteomic analyses. Using these methodologies, we identified fiber type-specific alterations and many potential biomarkers of muscle chronological aging and age-related pathologies.

Research activities

Immunohistological analyses performed with muscle biopsies indicated that: (1) healthy aging is associated with atrophy and deformation of myofibres (mostly type-II) and with slight accumulations of intramyocellular lipid droplets; (2) hypertension in the elderly is further linked with perturbations in muscle capillarization and mitochondrial oxidative activities; and (3) metabolic syndrome with changes in lipid profiles as revealed by molecular imaging. We also demonstrated that age-related increase in apoptosis in muscle is (i) not confined to myofibres, but (j) of significant importance in satellite cells, and (k) preponderant in capillary endothelial cells, which may alter the delivery of nutrients and oxygen and the removal of toxic metabolic products.

To better understand the mechanisms of aging, we have developed several differential proteomic approaches and settled for muscle ‘shot-gun’ proteomics and mass spectrometry molecular imaging to study unique cohorts of elderly subjects. Overall our investigations assessed more than 2500 proteins and identified nearly 100 (including 53 new) potential biomarkers of muscle chronological aging in Human. Our results indicate important modifications in cytosolic, mitochondrial and lipid energy metabolism, which may relate to dysfunctions in old muscle force generation. Some differentially expressed proteins were linked to the sarcomere and cytoskeleton, which may account for alterations in contractile properties. In line with muscle contraction, we also identified proteins related to calcium signalling. Muscle ageing was further characterized by the differential regulation of several proteins implicated in cytoprotection, detoxification and ion homeostasis. Notably, many of the differentially expressed proteins are central for proteostasis, including heat-shock proteins and proteins involved in proteolysis. To our knowledge, these studies describe the most extensive proteomic analysis of muscle aging in humans.