Fraker P J, Lill-Elghanian D A
Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USA.
J Nutr Health Aging. 2004;8(1):56-63.
Apoptosis plays a vital role in the elimination of anti-self clones, down regulation of immune responses and the killing of virally infected and malignant cells. There is ample evidence that as we age the immune system not only becomes less potent, but dysregulated which includes apoptotic dependent functions. Reductions in the production of naive T and B-cells, reduced cytolytic killing capacity, accumulation of larger numbers of malignant cells, enhanced inflammatory responses, etc., in the aged suggest that apoptosis is dysregulated. Changes in nutritional status can also alter apoptosis. A short period of zinc deficiency (ZD) in young adult mice greatly accelerated apoptosis among pre-B and pre-T cells by 50% to 300% providing a mechanistic explanation for the lymphopenia and thymic atrophy long associated with this and other nutritional deficiencies. Since apoptosis has been shown to be altered by aging and nutritional status, it seemed important to determine how ZD affected these processes in the aged mouse. It was quickly discovered that the pre-B cells were reduced by 80% in the 28 month aged mouse making further studies problematic. In marked contrast to suboptimal zinc, caloric restriction (CR) which when initiated in younger mice delayed the onset of autoimmunity and immunosenescence. CR appeared to also slow the aging of mitochondria and, thereby, reduced the release of reactive oxygen species that damage cells. Thus, it is probable that CR also helped maintain the integrity of mitochondria and apoptotic processes as mice aged. Though CR is not a very practical nutritional model for humans, the outcome of these studies reinforce the potential value of anti-oxidants in our diets. In contrast to their normal nutritional role some nutrients especially small amounts of free metals can induce apoptosis. There is considerable zinc in neurons. As will be discussed, a number of investigators think that this zinc is released during Alzheimer's, Parkinsons's, or brain injury and accelerates apoptosis in surrounding tissues causing greater damage. Data are discussed that indicate nanomoles of free zinc is, indeed, a potent inducer of apoptosis in a variety of tissues. In sum, there is no doubt that nutritional status as well as individual nutrients can modulate apoptosis and that their impact on cell death may become greater in the aged.
细胞凋亡在清除自身反应性克隆、下调免疫反应以及杀伤病毒感染细胞和恶性细胞方面发挥着至关重要的作用。有充分证据表明，随着年龄增长，免疫系统不仅功能变弱，而且会失调，这包括依赖细胞凋亡的功能。老年人体内幼稚T细胞和B细胞产生减少、细胞溶解杀伤能力降低、大量恶性细胞积累、炎症反应增强等，表明细胞凋亡失调。营养状况的改变也会影响细胞凋亡。年轻成年小鼠短期缺锌会使前B细胞和前T细胞中的细胞凋亡大幅加速50%至300%，这为长期以来与此及其他营养缺乏相关的淋巴细胞减少和胸腺萎缩提供了一种机制解释。由于细胞凋亡已被证明会因衰老和营养状况而改变，因此确定缺锌如何影响老年小鼠的这些过程似乎很重要。很快就发现，28个月大的老年小鼠中的前B细胞减少了80%，这使得进一步研究变得困难。与锌摄入不足形成鲜明对比的是，在年轻小鼠中开始的热量限制（CR）可延迟自身免疫和免疫衰老的发生。热量限制似乎还减缓了线粒体的衰老，从而减少了损伤细胞的活性氧的释放。因此，随着小鼠年龄增长，热量限制可能也有助于维持线粒体的完整性和细胞凋亡过程。尽管热量限制对人类来说不是一个非常实用的营养模型，但这些研究结果强化了我们饮食中抗氧化剂的潜在价值。与它们正常的营养作用相反，一些营养素，尤其是少量的游离金属，可诱导细胞凋亡。神经元中含有大量锌。正如将要讨论的，许多研究人员认为，在阿尔茨海默病、帕金森病或脑损伤期间，这种锌会释放出来，并加速周围组织的细胞凋亡，造成更大的损害。所讨论的数据表明，纳摩尔级的游离锌确实是多种组织中细胞凋亡的有效诱导剂。总之，毫无疑问，营养状况以及个别营养素可以调节细胞凋亡，而且它们对细胞死亡的影响在老年人中可能会更大。
