Neri Simona, Cattini Luca, Facchini Andrea, Pawelec Graham, Mariani Erminia
Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla Putti, IOR, Via di Barbiano 1/10, 40136 Bologna, Italy.
Exp Gerontol. 2004 Apr;39(4):499-505. doi: 10.1016/j.exger.2003.11.017.
Repair of mismatches in mammalian cell DNA is mediated by a complex of proteins that constitute the so-called mismatch repair system (MMR), the main post-replicative pathway for the correction of replication errors. Loss of MMR (as exemplified by germline mutations in some MMR genes, leading to hereditary non-polyposis colorectal cancer) results in increased mutation rates at both coding sequences and in non-coding regions such as microsatellites. In order to evaluate possible functional alterations of this repair system during ageing that could affect immune system efficiency, we studied microsatellite instability at five different loci interspersed in the genome (CD4, VWA31, Tpox, Fes/FPS and p53) in total DNA from T lymphocyte clones derived from hematopoietic stem cells, or peripheral T cells of young or elderly subjects. In addition, these clones had been maintained for different periods in vitro to represent a culture model of ageing. We observed increasing instability accumulating with increasing passages in culture, particularly in CD34+cell-derived clones, but no clear donor age relationship.
哺乳动物细胞DNA错配修复是由一组蛋白质复合体介导的，这些蛋白质构成了所谓的错配修复系统（MMR），这是纠正复制错误的主要复制后途径。MMR功能丧失（如某些MMR基因的种系突变导致遗传性非息肉病性结直肠癌）会导致编码序列和微卫星等非编码区域的突变率增加。为了评估衰老过程中该修复系统可能影响免疫系统效率的功能改变，我们研究了来自造血干细胞或年轻或老年受试者外周T细胞的T淋巴细胞克隆的总DNA中，散布于基因组的五个不同位点（CD4、VWA31、Tpox、Fes/FPS和p53）的微卫星不稳定性。此外，这些克隆在体外维持了不同的时间，以代表衰老的培养模型。我们观察到随着培养传代次数的增加，不稳定性增加，特别是在CD34+细胞衍生的克隆中，但没有明显的供体年龄关系。
