Mishto Michele, Santoro Aurelia, Bellavista Elena, Bonafé Massimiliano, Monti Daniela, Franceschi Claudio
Department of Experimental Pathology, University of Bologna, Via San Giacomo, 12, Bologna IT-40126, Italy.
Ageing Res Rev. 2003 Oct;2(4):419-32. doi: 10.1016/s1568-1637(03)00030-8.
Aging is a complex process which is accompanied with the decline and the reshaping of different functions of the body. In particular the immune system is characterized, during ageing (immunosenescence) by a remodeling of innate immunity (well preserved, up-regulated) and clonotypical immunity (severely altered) and by the occurrence of a chronic inflammatory process (inflammaging) which are, at least in part, genetically controlled. In this scenario, it can be anticipated that a crucial role is played by age-related structural and functional alterations and modifications of proteasomes and immunoproteasomes, the last being a key component of antigen processing and MHC class I antigen presentation. A variety of experimental data are available, suggesting that proteasomes are affected by age, and that in centenarians they are relatively preserved. On the contrary, few data are available on immunoproteasomes, likely as a consequence of the poverty of suitable cellular models. Lymphoblastoid cell lines from EBV immortalized B cells from old donors is envisaged as a possible model for the study of immunoproteasomes in humans and their changes with age. Thus, basic questions such as those related to possible consequences, for immune responses in infectious diseases and cancer, of age-related alterations of antigen processing and presenting, change with age of self-antigen repertoire, and the genetic basis of immunoproteasome activity and its change with age, remain largely unanswered.
衰老过程复杂，伴随着身体各项功能的衰退与重塑。特别是免疫系统在衰老过程（免疫衰老）中具有以下特点：固有免疫重塑（保存良好、上调）、克隆型免疫严重改变，以及慢性炎症过程（炎症衰老）的出现，这些至少部分受基因控制。在这种情况下，可以预期，与年龄相关的蛋白酶体和免疫蛋白酶体的结构与功能改变及修饰起着关键作用，后者是抗原加工和MHC I类抗原呈递的关键组成部分。现有各种实验数据表明，蛋白酶体受年龄影响，在百岁老人中相对保存较好。相反，关于免疫蛋白酶体的数据较少，这可能是由于缺乏合适的细胞模型。来自老年供体的EBV永生化B细胞的淋巴母细胞系被设想为研究人类免疫蛋白酶体及其随年龄变化的一种可能模型。因此，诸如与抗原加工和呈递的年龄相关改变对传染病和癌症免疫反应的可能影响、自身抗原库随年龄的变化以及免疫蛋白酶体活性的遗传基础及其随年龄的变化等基本问题，在很大程度上仍未得到解答。
