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A novel atlas of ge...
A novel atlas of gene expression in human skeletal muscle reveals molecular changes associated with aging
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- Su, Jing (author)
- Wellcome Trust Genome Campus Hinxton, European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England.
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- Ekman, Carl (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Skane Univ Hosp Malmo, S-20502 Malmo, Sweden.
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- Oskolkov, Nikolay (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Skane Univ Hosp Malmo, S-20502 Malmo, Sweden.
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- Lahti, Leo (author)
- Univ Helsinki, Dept Vet Biosci, FI-00014 Helsinki, Finland.
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- Ström, Kristoffer (author)
- Mittuniversitetet,Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Avdelningen för hälsovetenskap,Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Skane Univ Hosp Malmo, S-20502 Malmo, Sweden.,Swedish Winter Sports Research Center
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- Brazma, Alvis (author)
- Wellcome Trust Genome Campus Hinxton, European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England.
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Skane Univ Hosp Malmo, S-20502 Malmo, Sweden.
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- Rung, Johan (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Wellcome Trust Genome Campus Hinxton, European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England.;Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Rudbeck Lab, S-75185 Uppsala, Sweden.
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- Hansson, Ola (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Skane Univ Hosp Malmo, S-20502 Malmo, Sweden.
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Wellcome Trust Genome Campus Hinxton, European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England Genomik, diabetes och endokrinologi (creator_code:org_t)
- 2015-10-09
- 2015
- English.
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In: Skeletal Muscle. - : Springer Science and Business Media LLC. - 2044-5040. ; 5
- Related links:
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http://www.ncbi.nlm....
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https://skeletalmusc...
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https://portal.resea... (primary) (free)
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http://www.ncbi.nlm....
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http://dx.doi.org/10... (free)
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https://miun.diva-po... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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 x 10(-13)), AHNAK nucleoprotein, desmoyokin (AHNAK, p = 6.9 x 10(-12)), and histone deacetylase 4 (HDAC4, p = 4.0 x 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 x 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Idrottsvetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Sport and Fitness Sciences (hsv//eng)
Keyword
- Skeletal muscle
- Expression
- Microarray
- Aging
- Mitochondrial dysfunction
- Exercise
Publication and Content Type
- ref (subject category)
- art (subject category)
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