Proust J J, Quadri R A, Arbogast A, Phelouzat M A
Département de Gériatrie, Hôpitaux Universitaires de Genève, Université de Genève, Suisse.
Pathol Biol (Paris). 1996 Oct;44(8):729-36.
Aging is classically accompanied by a dysregulation of the immunologic machinery. As a consequence, the immune response developed in senescent organisms is usually inappropriate, often inefficient, sometimes aberrant, and potentially detrimental. The age-associated immune dysfunction may be implicated to some degree in the extreme susceptibility of the elderly to infection and neoplasia and may even participate in various aspects of senescence. The current understanding of the molecular mechanisms underlying immunosenescence is still fragmentary. The most extensively studied phenomenon is the progressive decline in the proliferative capacities of T lymphocytes with aging. The loss of proliferative potential in response to antigenic challenge is a characteristic feature of immune senescence. It is directly implicated in the emergence of the age-related immune deficiency. The purpose of this review is to show how the accumulation of various biochemical lesions with advancing age leads to the failure of a critical cell function, namely the activation-induced lymphocyte proliferation. The biochemical modifications responsible for the defect in transduction and execution of the proliferative signal are analyzed as a function of age. The multiple alterations observed on the various biochemical pathways may appear as a consequence of a unique deleterious mechanism more fundamentally related to the process of senescence such as the inability to cope with oxidative stress.
衰老通常伴随着免疫机制的失调。因此，衰老生物体中产生的免疫反应通常是不适当的，常常效率低下，有时异常，并且可能有害。与年龄相关的免疫功能障碍在一定程度上可能与老年人对感染和肿瘤的极度易感性有关，甚至可能参与衰老的各个方面。目前对免疫衰老潜在分子机制的理解仍然不完整。研究最广泛的现象是随着年龄增长T淋巴细胞增殖能力的逐渐下降。对抗原刺激的增殖潜能丧失是免疫衰老的一个特征。它直接与年龄相关免疫缺陷的出现有关。这篇综述的目的是展示随着年龄增长各种生化损伤的积累如何导致关键细胞功能的失败，即激活诱导的淋巴细胞增殖。作为年龄的函数，分析了负责增殖信号转导和执行缺陷的生化修饰。在各种生化途径上观察到的多种改变可能是由于一种更根本地与衰老过程相关的独特有害机制导致的结果，例如无法应对氧化应激。
