title: Proteomics of muscle chronological ageing in post-menopausal women.
abstract: BACKGROUND
  Muscle ageing contributes to both loss of functional autonomy and increased morbidity. Muscle atrophy accelerates after 50 years of age, but the mechanisms involved are complex and likely result from the alteration of a variety of interrelated functions. In order to better understand the molecular mechanisms underlying muscle chronological ageing in human, we have undertaken a top-down differential proteomic approach to identify novel biomarkers after the fifth decade of age.
  
  
  RESULTS
  Muscle samples were compared between adult (56 years) and old (78 years) post-menopausal women. In addition to total muscle extracts, low-ionic strength extracts were investigated to remove high abundance myofibrillar proteins and improve the detection of low abundance proteins. Two-dimensional gel electrophoreses with overlapping IPGs were used to improve the separation of muscle proteins. Overall, 1919 protein spots were matched between all individuals, 95 were differentially expressed and identified by mass spectrometry, and they corresponded to 67 different proteins. Our results suggested important modifications in cytosolic, mitochondrial and lipid energy metabolism, which may relate to dysfunctions in old muscle force generation. A fraction of the differentially expressed proteins were linked to the sarcomere and cytoskeleton (myosin light-chains, troponin T, ankyrin repeat domain-containing protein-2, vinculin, four and a half LIM domain protein-3), which may account for alterations in contractile properties. In line with muscle contraction, we also identified proteins related to calcium signal transduction (calsequestrin-1, sarcalumenin, myozenin-1, annexins). Muscle ageing was further characterized by the differential regulation of several proteins implicated in cytoprotection (catalase, peroxiredoxins), ion homeostasis (carbonic anhydrases, selenium-binding protein 1) and detoxification (aldo-keto reductases, aldehyde dehydrogenases). Notably, many of the differentially expressed proteins were central for proteostasis, including heat shock proteins and proteins involved in proteolysis (valosin-containing protein, proteasome subunit beta type-4, mitochondrial elongation factor-Tu).
  
  
  CONCLUSIONS
  This study describes the most extensive proteomic analysis of muscle ageing in humans, and identified 34 new potential biomarkers. None of them were previously recognized as differentially expressed in old muscles, and each may represent a novel starting point to elucidate the mechanisms of muscle chronological ageing in humans.
authors.affiliation: INRA, UMR 1019, Centre de Recherche en Nutrition Humaine, Université d'Auvergne, F-63122, Saint Genès Champanelle, France. marine.gueugneau@uclouvain.be.|Clermont Université, Université d'Auvergne, F-63000, Clermont-Ferrand, France. marine.gueugneau@uclouvain.be.|Pôle Endocrinologie, Diabétologie et Nutrition, Institut de Recherches Expérimentales et Cliniques, Université Catholique de Louvain, B-1200, Brussels, Belgium. marine.gueugneau@uclouvain.be.
authors.forename: Marine
authors.initials: M
authors.lastname: Gueugneau
authors.affiliation: INRA, UMR 1019, Centre de Recherche en Nutrition Humaine, Université d'Auvergne, F-63122, Saint Genès Champanelle, France. cecile.coudy@clermont.inra.fr.|Clermont Université, Université d'Auvergne, F-63000, Clermont-Ferrand, France. cecile.coudy@clermont.inra.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Coudy-Gandilhon
authors.affiliation: INRA, UMR 1019, Centre de Recherche en Nutrition Humaine, Université d'Auvergne, F-63122, Saint Genès Champanelle, France. ophelie.gourbeyre@gmail.com.|Clermont Université, Université d'Auvergne, F-63000, Clermont-Ferrand, France. ophelie.gourbeyre@gmail.com.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Gourbeyre
authors.affiliation: INRA, Plateforme d'Exploration du Métabolisme, Composante Protéique, F-63122, Saint Genès Champanelle, France. cchambon@clermont.inra.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chambon
authors.affiliation: INRA, UMR 1019, Centre de Recherche en Nutrition Humaine, Université d'Auvergne, F-63122, Saint Genès Champanelle, France. lydie.combaret@clermont.inra.fr.|Clermont Université, Université d'Auvergne, F-63000, Clermont-Ferrand, France. lydie.combaret@clermont.inra.fr.
authors.forename: Lydie
authors.initials: L
authors.lastname: Combaret
authors.affiliation: INRA, UMR 1019, Centre de Recherche en Nutrition Humaine, Université d'Auvergne, F-63122, Saint Genès Champanelle, France. cecile.polge@clermont.inra.fr.|Clermont Université, Université d'Auvergne, F-63000, Clermont-Ferrand, France. cecile.polge@clermont.inra.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Polge
authors.affiliation: INRA, UMR 1019, Centre de Recherche en Nutrition Humaine, Université d'Auvergne, F-63122, Saint Genès Champanelle, France. daniel.taillandier@clermont.inra.fr.|Clermont Université, Université d'Auvergne, F-63000, Clermont-Ferrand, France. daniel.taillandier@clermont.inra.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Taillandier
authors.affiliation: INRA, UMR 1019, Centre de Recherche en Nutrition Humaine, Université d'Auvergne, F-63122, Saint Genès Champanelle, France. didier.attaix@clermont.inra.fr.|Clermont Université, Université d'Auvergne, F-63000, Clermont-Ferrand, France. didier.attaix@clermont.inra.fr.
authors.forename: Didier
authors.initials: D
authors.lastname: Attaix
authors.affiliation: UPMC Université Paris 06, UMR 8256, Biological Adaptation and Ageing - IBPS, CNRS-UMR 8256, INSERM U1164, Sorbonne Universités, F-75005, Paris, France. bertrand.friguet@snv.jussieu.fr.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.affiliation: Department of Internal Medicine, Section of Gerontology and Geriatrics, VU University Medical Center, Amsterdam, The Netherlands. a.maier@vumc.nl.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Maier
authors.affiliation: Institut de Myologie, Centre de Recherches en Myologie UMR 974 76, INSERM U974, CNRS FRE 3617, Sorbonne Universités, UPMC Université Paris 06, F-75013, Paris, France. gillian.butler-browne@upmc.fr.
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.affiliation: INRA, UMR 1019, Centre de Recherche en Nutrition Humaine, Université d'Auvergne, F-63122, Saint Genès Champanelle, France. daniel.bechet@clermont.inra.fr.|Clermont Université, Université d'Auvergne, F-63000, Clermont-Ferrand, France. daniel.bechet@clermont.inra.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Béchet
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003603:Cytotoxins / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009132:Muscles / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress; D017698:Postmenopause / Q000378:metabolism / Q000502:physiology*; D059748:Proteolysis; D040901:Proteomics; D012518:Sarcomeres / Q000378:metabolism; D055948:Sarcopenia / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D003603:Cytotoxins