Aging and genome maintenance
Aging and genome maintenance
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DOI：
10.1196/annals.1323.007
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Dollé, MET
中科院分区：
文献类型：
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作者：
Vijg, J;Busuttil, RA;Dollé, MET
体细胞基因组的不稳定性是衰老的主要随机机制。使用染色体整合lacZ突变靶基因的转基因小鼠模型，我们发现突变以器官和组织特异性的速率随着年龄的增长而积累。此外，年龄累积的突变谱被发现在不同器官之间有很大差异;虽然最初相似，但不同组织的突变谱在一生中显着不同。为了解释基因组的不稳定性，这是固有的随机性，可以在老化的一个因果因素，它提出，随机诱导的突变可能会对基因调控的正常模式产生不利影响，导致在不同阶段的细胞在退化的轨迹马赛克，最终导致细胞死亡或肿瘤转化。为了直接解决这个问题，我们证明，现在可以分析从老年和年轻组织中分离的单细胞，用于基因表达的特定改变。
Genomic instability in somatic cells has been implicated as a major stochastic mechanism of aging. Using a transgenic mouse model with chromosomally integrated lacZ mutational target genes, we found mutations to accumulate with age at an organ- and tissue-specific rate. Also the spectrum of age-accumulated mutations was found to differ greatly from organ to organ; while initially similar, mutation spectra of different tissues diverged significantly over the lifetime. To explain how genomic instability, which is inherently stochastic, can be a causal factor in aging, it is proposed that randomly induced mutations may adversely affect normal patterns of gene regulation, resulting in a mosaic of cells at various stages on a trajectory of degeneration, eventually resulting in cell death or neoplastic transformation. To directly address this question we demonstrate that it is now possible to analyze single cells, isolated from old and young tissues, for specific alterations in gene expression.