Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs.
Genome-wide DNA methylation changes in skeletal muscle between young and middle-aged pigs.
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年轻和中年猪骨骼肌的全基因组 DNA 甲基化变化
DOI：
10.1186/1471-2164-15-653
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发表时间：
2014-08-05
期刊：
影响因子：
4.4
通讯作者：
Li M
中科院分区：
文献类型：
--
作者：
Jin L;Jiang Z;Xia Y;Lou P;Chen L;Wang H;Bai L;Xie Y;Liu Y;Li W;Zhong B;Shen J;Jiang A;Zhu L;Wang J;Li X;Li M
哺乳动物骨骼肌中与骨骼肌相关的生理、生化和功能变化已显示在寿命的中点开始。然而，在肌肉衰老过程的这个转折点期间发生的DNA甲基化的潜在变化尚未阐明。为了探索骨骼肌中与年龄相关的基因组甲基化变化，我们以青年（0.5岁）和中年（7岁）猪为模型，使用甲基化DNA免疫沉淀测序方法调查背最长肌中全基因组DNA甲基化。我们观察到与年轻组相比，中年猪骨骼肌基因体区域的DNA甲基化有整体丢失的趋势。我们使用微阵列分析确定了背最长肌全基因组基因表达模式，并使用DMR（差异甲基化区域）-mRNA对进行了相关性分析，我们发现基因体内甲基化水平的变化与基因表达之间存在显著的负相关性。此外，我们发现了许多基因，这些基因显示出与年龄相关的甲基化变化，这些变化可能参与衰老过程。使用亚硫酸氢盐测序PCR确认这些基因的甲基化状态。在中年猪中表现出低甲基化基因体的基因在各种蛋白质水解和蛋白质分解代谢过程中过度表达，表明这些基因在年龄相关的肌肉萎缩中起重要作用。此外，与肿瘤发生相关的基因在甲基化和表达水平上表现出与年龄相关的差异，这表明与年龄增加相关的疾病风险增加。本研究对衰老猪骨骼肌全基因组DNA甲基化模式进行了全面分析。我们的研究结果将为衰老研究提供宝贵的资源，促进猪作为人类衰老研究的模式生物，并加速衰老研究中比较动物模型的发展。本文的在线版本（doi：10.1186/1471-2164-15-653）包含补充材料，可供授权用户使用。
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. 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. 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. 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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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
56.9
作者：
Giraldez, AJ;Mishima, Y;Schier, AF
通讯作者：
Schier, AF
DOI：
10.1073/pnas.0908131106
发表时间：
2009-11-03
影响因子：
11.1
作者：
Hammell, Christopher M.;Karp, Xantha;Ambros, Victor
通讯作者：
Ambros, Victor
DOI：
10.1126/science.1164899
发表时间：
2009-04-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bethke A;Fielenbach N;Wang Z;Mangelsdorf DJ;Antebi A
通讯作者：
Antebi A
影响因子：
46.9
作者：
Friedlaender, Marc R.;Chen, Wei;Rajewsky, Nikolaus
通讯作者：
Rajewsky, Nikolaus