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Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs

BACKGROUND: Age-related physiological, biochemical and functional changes in mammalian skeletal muscle have been shown to begin at the mid-point of the lifespan. However, the underlying changes in DNA methylation that occur during this turning point of the muscle aging process have not been clarifie...

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Autores principales: Jin, Long, Jiang, Zhi, Xia, Yudong, Lou, Ping’er, Chen, Lei, Wang, Hongmei, Bai, Lu, Xie, Yanmei, Liu, Yihui, Li, Wei, Zhong, Bangsheng, Shen, Junfang, Jiang, An’an, Zhu, Li, Wang, Jinyong, Li, Xuewei, Li, Mingzhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147169/
https://www.ncbi.nlm.nih.gov/pubmed/25096499
http://dx.doi.org/10.1186/1471-2164-15-653
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author Jin, Long
Jiang, Zhi
Xia, Yudong
Lou, Ping’er
Chen, Lei
Wang, Hongmei
Bai, Lu
Xie, Yanmei
Liu, Yihui
Li, Wei
Zhong, Bangsheng
Shen, Junfang
Jiang, An’an
Zhu, Li
Wang, Jinyong
Li, Xuewei
Li, Mingzhou
author_facet Jin, Long
Jiang, Zhi
Xia, Yudong
Lou, Ping’er
Chen, Lei
Wang, Hongmei
Bai, Lu
Xie, Yanmei
Liu, Yihui
Li, Wei
Zhong, Bangsheng
Shen, Junfang
Jiang, An’an
Zhu, Li
Wang, Jinyong
Li, Xuewei
Li, Mingzhou
author_sort Jin, Long
collection PubMed
description BACKGROUND: Age-related physiological, biochemical and functional changes in mammalian skeletal muscle have been shown to begin at the mid-point of the lifespan. However, the underlying changes in DNA methylation that occur during this turning point of the muscle aging process have not been clarified. To explore age-related genomic methylation changes in skeletal muscle, we employed young (0.5 years old) and middle-aged (7 years old) pigs as models to survey genome-wide DNA methylation in the longissimus dorsi muscle using a methylated DNA immunoprecipitation sequencing approach. RESULTS: We observed a tendency toward a global loss of DNA methylation in the gene-body region of the skeletal muscle of the middle-aged pigs compared with the young group. We determined the genome-wide gene expression pattern in the longissimus dorsi muscle using microarray analysis and performed a correlation analysis using DMR (differentially methylated region)-mRNA pairs, and we found a significant negative correlation between the changes in methylation levels within gene bodies and gene expression. Furthermore, we identified numerous genes that show age-related methylation changes that are potentially involved in the aging process. The methylation status of these genes was confirmed using bisulfite sequencing PCR. The genes that exhibited a hypomethylated gene body in middle-aged pigs were over-represented in various proteolysis and protein catabolic processes, suggesting an important role for these genes in age-related muscle atrophy. In addition, genes associated with tumorigenesis exhibited aged-related differences in methylation and expression levels, suggesting an increased risk of disease associated with increased age. CONCLUSIONS: This study provides a comprehensive analysis of genome-wide DNA methylation patterns in aging pig skeletal muscle. Our findings will serve as a valuable resource in aging studies, promoting the pig as a model organism for human aging research and accelerating the development of comparative animal models in aging research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-653) contains supplementary material, which is available to authorized users.
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spelling pubmed-41471692014-09-02 Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs Jin, Long Jiang, Zhi Xia, Yudong Lou, Ping’er Chen, Lei Wang, Hongmei Bai, Lu Xie, Yanmei Liu, Yihui Li, Wei Zhong, Bangsheng Shen, Junfang Jiang, An’an Zhu, Li Wang, Jinyong Li, Xuewei Li, Mingzhou BMC Genomics Research Article BACKGROUND: Age-related physiological, biochemical and functional changes in mammalian skeletal muscle have been shown to begin at the mid-point of the lifespan. However, the underlying changes in DNA methylation that occur during this turning point of the muscle aging process have not been clarified. To explore age-related genomic methylation changes in skeletal muscle, we employed young (0.5 years old) and middle-aged (7 years old) pigs as models to survey genome-wide DNA methylation in the longissimus dorsi muscle using a methylated DNA immunoprecipitation sequencing approach. RESULTS: We observed a tendency toward a global loss of DNA methylation in the gene-body region of the skeletal muscle of the middle-aged pigs compared with the young group. We determined the genome-wide gene expression pattern in the longissimus dorsi muscle using microarray analysis and performed a correlation analysis using DMR (differentially methylated region)-mRNA pairs, and we found a significant negative correlation between the changes in methylation levels within gene bodies and gene expression. Furthermore, we identified numerous genes that show age-related methylation changes that are potentially involved in the aging process. The methylation status of these genes was confirmed using bisulfite sequencing PCR. The genes that exhibited a hypomethylated gene body in middle-aged pigs were over-represented in various proteolysis and protein catabolic processes, suggesting an important role for these genes in age-related muscle atrophy. In addition, genes associated with tumorigenesis exhibited aged-related differences in methylation and expression levels, suggesting an increased risk of disease associated with increased age. CONCLUSIONS: This study provides a comprehensive analysis of genome-wide DNA methylation patterns in aging pig skeletal muscle. Our findings will serve as a valuable resource in aging studies, promoting the pig as a model organism for human aging research and accelerating the development of comparative animal models in aging research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-653) contains supplementary material, which is available to authorized users. BioMed Central 2014-08-05 /pmc/articles/PMC4147169/ /pubmed/25096499 http://dx.doi.org/10.1186/1471-2164-15-653 Text en © Jin et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Jin, Long
Jiang, Zhi
Xia, Yudong
Lou, Ping’er
Chen, Lei
Wang, Hongmei
Bai, Lu
Xie, Yanmei
Liu, Yihui
Li, Wei
Zhong, Bangsheng
Shen, Junfang
Jiang, An’an
Zhu, Li
Wang, Jinyong
Li, Xuewei
Li, Mingzhou
Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs
title Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs
title_full Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs
title_fullStr Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs
title_full_unstemmed Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs
title_short Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs
title_sort genome-wide dna methylation changes in skeletal muscle between young and middle-aged pigs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147169/
https://www.ncbi.nlm.nih.gov/pubmed/25096499
http://dx.doi.org/10.1186/1471-2164-15-653
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