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Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle.

Pöllänen E, Fey V, Törmäkangas T, Ronkainen PH, Taaffe DR, Takala T, Koskinen S, Cheng S, Puolakka J, Kujala UM, Suominen H, Sipilä S, Kovanen V - Age (Dordr) (2010)

Bottom Line: The analysis revealed transcriptional regulation of 49 GO/KEGG categories.Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment.Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness.

View Article: PubMed Central - PubMed

Affiliation: Gerontology Research Centre, University Jyväskylä, Jyväskylä, Finland. eija.pollanen@jyu.fi

ABSTRACT
At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50-57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in "response to contraction"-category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria.

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Related in: MedlinePlus

Graphical view of the cluster structure within each cluster (CL #1–CL #8). Each line represents the mean fold change (FC) of a single gene
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Fig1: Graphical view of the cluster structure within each cluster (CL #1–CL #8). Each line represents the mean fold change (FC) of a single gene

Mentions: Differentially expressed genes were defined as genes that differed between follow-up and baseline samples within a study group with statistical threshold p value <0.05 and /FC/ >1.2. These thresholds led to the discovery of 665 genes. In the PT group, 328 genes were upregulated and 182 downregulated, whereas in the HRT group, 34 genes were upregulated and 20 downregulated. The corresponding numbers for the CO group were 91 and 70, respectively. A non-redundant list of differentially expressed genes was used in the analysis of co-regulated gene clusters. Genes were sorted into eight significant and consistent clusters (Fig. 1, Table 1), which showed either study group-specific regulation or regulation into the same direction within all study groups. As seen in Fig. 1, genes within each cluster had a highly consistent expression pattern forming congruent cluster structure. The complete list of genes belonging to each cluster is presented in Table S1 as supporting information. For clarity, the official or commonly used acronym for gene names are used in the text and complete gene names with proper annotation are provided as supporting information in Table S2.Fig. 1


Power training and postmenopausal hormone therapy affect transcriptional control of specific co-regulated gene clusters in skeletal muscle.

Pöllänen E, Fey V, Törmäkangas T, Ronkainen PH, Taaffe DR, Takala T, Koskinen S, Cheng S, Puolakka J, Kujala UM, Suominen H, Sipilä S, Kovanen V - Age (Dordr) (2010)

Graphical view of the cluster structure within each cluster (CL #1–CL #8). Each line represents the mean fold change (FC) of a single gene
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2926854&req=5

Fig1: Graphical view of the cluster structure within each cluster (CL #1–CL #8). Each line represents the mean fold change (FC) of a single gene
Mentions: Differentially expressed genes were defined as genes that differed between follow-up and baseline samples within a study group with statistical threshold p value <0.05 and /FC/ >1.2. These thresholds led to the discovery of 665 genes. In the PT group, 328 genes were upregulated and 182 downregulated, whereas in the HRT group, 34 genes were upregulated and 20 downregulated. The corresponding numbers for the CO group were 91 and 70, respectively. A non-redundant list of differentially expressed genes was used in the analysis of co-regulated gene clusters. Genes were sorted into eight significant and consistent clusters (Fig. 1, Table 1), which showed either study group-specific regulation or regulation into the same direction within all study groups. As seen in Fig. 1, genes within each cluster had a highly consistent expression pattern forming congruent cluster structure. The complete list of genes belonging to each cluster is presented in Table S1 as supporting information. For clarity, the official or commonly used acronym for gene names are used in the text and complete gene names with proper annotation are provided as supporting information in Table S2.Fig. 1

Bottom Line: The analysis revealed transcriptional regulation of 49 GO/KEGG categories.Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment.Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness.

View Article: PubMed Central - PubMed

Affiliation: Gerontology Research Centre, University Jyväskylä, Jyväskylä, Finland. eija.pollanen@jyu.fi

ABSTRACT
At the moment, there is no clear molecular explanation for the steeper decline in muscle performance after menopause or the mechanisms of counteractive treatments. The goal of this genome-wide study was to identify the genes and gene clusters through which power training (PT) comprising jumping activities or estrogen containing hormone replacement therapy (HRT) may affect skeletal muscle properties after menopause. We used musculus vastus lateralis samples from early stage postmenopausal (50-57 years old) women participating in a yearlong randomized double-blind placebo-controlled trial with PT and HRT interventions. Using microarray platform with over 24,000 probes, we identified 665 differentially expressed genes. The hierarchical clustering method was used to assort the genes. Additionally, enrichment analysis of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was carried out to clarify whether assorted gene clusters are enriched with particular functional categories. The analysis revealed transcriptional regulation of 49 GO/KEGG categories. PT upregulated transcription in "response to contraction"-category revealing novel candidate genes for contraction-related regulation of muscle function while HRT upregulated gene expression related to functionality of mitochondria. Moreover, several functional categories tightly related to muscle energy metabolism, development, and function were affected regardless of the treatment. Our results emphasize that during the early stages of the postmenopause, muscle properties are under transcriptional modulation, which both PT and HRT partially counteract leading to preservation of muscle power and potentially reducing the risk for aging-related muscle weakness. More specifically, PT and HRT may function through improving energy metabolism, response to contraction as well as by preserving functionality of the mitochondria.

Show MeSH
Related in: MedlinePlus