title: A novel atlas of gene expression in human skeletal muscle reveals molecular changes associated with aging.
abstract: BACKGROUND
  Although high-throughput studies of gene expression have generated large amounts of data, most of which is freely available in public archives, the use of this valuable resource is limited by computational complications and non-homogenous annotation. To address these issues, we have performed a complete re-annotation of public microarray data from human skeletal muscle biopsies and constructed a muscle expression compendium consisting of nearly 3000 samples. The created muscle compendium is a publicly available resource including all curated annotation. Using this data set, we aimed to elucidate the molecular mechanism of muscle aging and to describe how physical exercise may alleviate negative physiological effects.
  
  
  RESULTS
  We find 957 genes to be significantly associated with aging (p < 0.05, FDR = 5 %, n = 361). Aging was associated with perturbation of many central metabolic pathways like mitochondrial function including reduced expression of genes in the ATP synthase, NADH dehydrogenase, cytochrome C reductase and oxidase complexes, as well as in glucose and pyruvate processing. Among the genes with the strongest association with aging were H3 histone, family 3B (H3F3B, p = 3.4 × 10(-13)), AHNAK nucleoprotein, desmoyokin (AHNAK, p = 6.9 × 10(-12)), and histone deacetylase 4 (HDAC4, p = 4.0 × 10(-9)). We also discover genes previously not linked to muscle aging and metabolism, such as fasciculation and elongation protein zeta 2 (FEZ2, p = 2.8 × 10(-8)). Out of the 957 genes associated with aging, 21 (p < 0.001, false discovery rate = 5 %, n = 116) were also associated with maximal oxygen consumption (VO2MAX). Strikingly, 20 out of those 21 genes are regulated in opposite direction when comparing increasing age with increasing VO2MAX.
  
  
  CONCLUSIONS
  These results support that mitochondrial dysfunction is a major age-related factor and also highlight the beneficial effects of maintaining a high physical capacity for prevention of age-related sarcopenia.
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Trust Genome Campus Hinxton, Cambridge, CB10 1SD UK.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital Malmö, Lund University, Malmö, 20502 Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Ekman
authors.affiliation: Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital Malmö, Lund University, Malmö, 20502 Sweden.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Oskolkov
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, PO Box 66, FI-00014 Helsinki, Finland.
authors.forename: Leo
authors.initials: L
authors.lastname: Lahti
authors.affiliation: Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital Malmö, Lund University, Malmö, 20502 Sweden.|Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, SE-83125 Östersund, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Ström
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Trust Genome Campus Hinxton, Cambridge, CB10 1SD UK.
authors.forename: Alvis
authors.initials: A
authors.lastname: Brazma
authors.affiliation: Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital Malmö, Lund University, Malmö, 20502 Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Trust Genome Campus Hinxton, Cambridge, CB10 1SD UK.|Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Rung
authors.affiliation: Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital Malmö, Lund University, Malmö, 20502 Sweden.
authors.forename: Ola
authors.identifier: 0000-0002-7394-7639
authors.initials: O
authors.lastname: Hansson
keywords: Aging; Exercise; Expression; Microarray; Mitochondrial dysfunction; Skeletal muscle