近日,，國際著名雜志PNAS上的一篇研究報告中，科研人員發(fā)現(xiàn)了所謂的“表觀基因組”——即一股DNA上的微小化學修飾的集合——可以把新生兒的DNA和老年人的DNA區(qū)分開來,。
Manel Esteller及其同事比較了一名103歲老年男子和一名新生男嬰的的DNA樣本,，檢索了遺傳修飾模式的能說明問題的差異。在每個例子中,，這組科研人員發(fā)現(xiàn)了1600多萬個位置,，DNA在這里通過一個稱為甲基化的過程而被修飾，甲基化阻礙了基因轉(zhuǎn)錄,。但是新生兒DNA的全部可能的位置有大約80%被甲基化了,，而百歲以上老人的DNA只有73%的位置被甲基化。
在總體上,，百歲老人的DNA的甲基化區(qū)域比新生兒少50萬個,，這提示百歲老人存在不適當?shù)幕蜣D(zhuǎn)錄模式。這組作者把他們的分析延伸以納入更大的一群新生兒和90到99歲的老人的DNA,，結(jié)果發(fā)現(xiàn)了90到99歲老人的DNA甲基化出現(xiàn)了類似的減少,。此外，來自中年人的DNA表明了甲基化水平下降到介于這兩個極端年齡之間的水平,。這組作者說,，這些結(jié)果支持了一個衰老模型，即表觀基因組的小變化——諸如DNA的甲基化狀態(tài)——可以隨著時間推移而積累,，并且導致基因表達和細胞功能的更廣泛的變化,。（生物谷Bioon.com）
doi:10.1073/pnas.1120658109
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Distinct DNA methylomes of newborns and centenarians
Holger Heyna,1, Ning Lib,c,1, Humberto J. Ferreiraa,d, Sebastian Morana, David G. Pisanoe, Antonio Gomeza, Javier Dieza, Jose V. Sanchez-Muta, Fernando Setiena, F. Javier Carmonaa, Annibale A. Pucaf,g, Sergi Sayolsa, Miguel A. Pujanah, Jordi Serra-Musachh, Isabel Iglesias-Platasi, Francesc Formigaj, Agustin F. Fernandezk, Mario F. Fragak,l, Simon C. Heathm, Alfonso Valenciae, Ivo G. Gutm, Jun Wangn,o,2, and Manel Estellera,p,q,2
Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine—phosphate—guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.
