Schindowski K, Leutner S, Müller W E, Eckert A
Institute of Pharmacology, Biocenter, Johann Wolfgang-Goethe- University, Frankfurt am Main, Germany.
Neurobiol Aging. 2000 Sep-Oct;21(5):661-70. doi: 10.1016/s0197-4580(00)00171-8.
Apoptosis seems to be involved in immunosenescence associated with aging. Moreover, in lymphocytes (PBL) of patients with Alzheimer's disease, an increased susceptibility to the apoptotic pathway has been described possibly due to impaired protection of oxidative stress. Accordingly, it seemed to be of particular interest to investigate the contribution of normal aging to the susceptibility from human lymphocytes to programmed cell death. We could show that PBL from elderly individuals (>60 years) accumulate apoptosing cells to a significant higher extent in spontaneous and activation-induced cell death compared to younger controls (<35 years). Treatment with the oxidative stressor 2-deoxy-D-ribose or with agonistic-CD95-antibody pronounced this effect even more implicating a higher sensitivity to reactive oxygen species and a higher functional CD95 expression, respectively. In addition, expression of the activation markers HLA-DR and CD95 was significantly increased in CD3+-cells of aged subjects, while expression of CD25 did not seem to be affected by age. Expression of Bcl-2 was increased in aging and correlated with the number of apoptotic cells.
细胞凋亡似乎与衰老相关的免疫衰老有关。此外，在阿尔茨海默病患者的淋巴细胞（外周血淋巴细胞）中，可能由于氧化应激保护受损，对凋亡途径的易感性增加。因此，研究正常衰老对人类淋巴细胞对程序性细胞死亡易感性的影响似乎特别有意义。我们可以证明，与年轻对照组（<35岁）相比，老年个体（>60岁）的外周血淋巴细胞在自发和激活诱导的细胞死亡中积累凋亡细胞的程度明显更高。用氧化应激剂2-脱氧-D-核糖或激动性CD95抗体处理进一步加剧了这种效应，分别表明对活性氧的更高敏感性和更高的功能性CD95表达。此外，老年受试者CD3+细胞中激活标志物HLA-DR和CD95的表达显著增加，而CD25的表达似乎不受年龄影响。Bcl-2的表达在衰老过程中增加，并与凋亡细胞数量相关。
