A novel atlas of gene expression in human skeletal muscle reveals molecular changes associated with aging

Skeletal Muscle

Ola Hansson⁴  Johan Rung⁵  Leif Groop⁴  Alvis Brazma¹  Kristoffer Ström²  Leo Lahti³  Nikolay Oskolkov⁴  Carl Ekman⁴  Jing Su¹ 

[1] European Molecular Biology Laboratory—European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, Wellcome Trust Genome Campus, UK;Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, SE-83125, Sweden;Department of Veterinary Biosciences, University of Helsinki, Helsinki, FI-00014, Finland;Lund University Diabetes Center, Department of Clinical Sciences, Diabetes and Endocrinology, Skåne University Hospital Malmö, Lund University, Malmö 20502, Sweden;Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala, 751 85, Sweden

关键词: Exercise;    Mitochondrial dysfunction;    Aging;    Microarray;    Expression;    Skeletal muscle;   

Others  :  1231176
DOI  :  10.1186/s13395-015-0059-1

 received in 2015-07-02, accepted in 2015-09-28,  发布年份 2015

【 摘 要 】

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 (VO _2MAX ). Strikingly, 20 out of those 21 genes are regulated in opposite direction when comparing increasing age with increasing VO _2MAX .

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.

【 授权许可】

   
2015 Su et al.

【 图 表 】

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