At first glance, longevity and immunity appear to be different traits that have not much in common except the fact that the immune system promotes survival upon pathogenic infection. Substantial evidence however points to a molecularly intertwined relationship between the immune system and ageing. Although this link is well-known throughout the animal kingdom, its genetic basis is complex and still poorly understood. To address this question, we here provide a compilation of all genes concomitantly known to be involved in immunity and ageing in humans and three well-studied model organisms, the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the house mouse Mus musculus. By analysing human orthologs among these species, we identified 7 evolutionarily conserved signalling cascades, the insulin/TOR network, three MAPK (ERK, p38, JNK), JAK/STAT, TGF-β, and Nf-κB pathways that act pleiotropically on ageing and immunity. We review current evidence for these pathways linking immunity and lifespan, and their role in the detrimental dysregulation of the immune system with age, known as immunosenescence. We argue that the phenotypic effects of these pathways are often context-dependent and vary, for example, between tissues, sexes, and types of pathogenic infection. Future research therefore needs to explore a higher temporal, spatial and environmental resolution to fully comprehend the connection between ageing and immunity.

中文翻译：

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连接衰老和免疫力的基因和途径中的功能保守

乍一看，长寿和免疫似乎是不同的特征，除了免疫系统在病原体感染时能促进生存之外，没有什么共同点。然而，大量证据表明，免疫系统与衰老之间存在分子上的纠缠关系。尽管这种联系在整个动物界都广为人知，但其遗传基础却很复杂，仍然了解甚少。为了解决这个问题，我们在这里提供了所有已知与人类和三种经过充分研究的模型生物体中的免疫力和衰老有关的基因的汇编，即线虫，秀丽隐杆线虫，果蝇Drosophila melanogaster和家鼠Mus musculus。 。通过分析这些物种中的人类直系同源物，我们确定了7个进化上保守的信号级联，即胰岛素/ TOR网络，三种MAPK（ERK，p38，JNK），JAK / STAT，TGF-β和Nf-κB通路对衰老和免疫功能具有多效性。我们回顾了有关这些将免疫力和寿命联系起来的途径的最新证据，以及它们在随着年龄增长而对免疫系统造成的有害失调中所起的作用，称为免疫衰老。我们认为，这些途径的表型效应通常取决于上下文，并且例如在组织，性别和病原体感染类型之间有所不同。因此，未来的研究需要探索更高的时间，空间和环境分辨率，以充分理解衰老与免疫力之间的联系。以及它们在随着年龄增长对免疫系统造成有害失调中的作用，称为免疫衰老。我们认为，这些途径的表型效应通常取决于上下文，并且例如在组织，性别和病原体感染类型之间有所不同。因此，未来的研究需要探索更高的时间，空间和环境分辨率，以充分理解衰老与免疫力之间的联系。以及它们在随着年龄增长对免疫系统造成有害失调中的作用，称为免疫衰老。我们认为，这些途径的表型效应通常是与环境相关的，并且例如在组织，性别和病原体感染类型之间有所不同。因此，未来的研究需要探索更高的时间，空间和环境分辨率，以充分理解衰老与免疫力之间的联系。