Raz Yotam, Guerrero-Ros Ignacio, Maier Andrea, Slagboom P Eline, Atzmon Gil, Barzilai Nir, Macian Fernando
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
Department of Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
J Gerontol A Biol Sci Med Sci. 2017 Sep 1;72(9):1201-1206. doi: 10.1093/gerona/glx020.
As with many other tissues and organs, the immune system is also affected by age. Immunosenescence is characterized by a decreased ability of immune cells to mount a productive response upon exposure to new antigens. Several studies have reported that members of families with exceptional longevity show improved immune function, which might contribute to the increased life- and health-span observed in those families. Autophagy is a catabolic process that delivers cytoplasmic material to the lysosomes for degradation. Defective autophagy is known to be associated with age in several cell types and tissues and its dysregulation is related to age-associated diseases. In T-cells, autophagy has an essential role in modulating protein and organelle homeostasis and in the regulation of activation-induced responses. In this study, using two different cohorts of individuals belonging to families with exceptional longevity, we show that CD4+ T-cells isolated from the offspring of parents with exceptional longevity show improved activation-induced autophagic activity compared with age-matched controls. Interestingly, increased autophagy is positively correlated with increased interferon-γ production. In conclusion, autophagy appears to be better maintained in members of families with extended longevity and positively correlates with improved T-cell function.
与许多其他组织和器官一样，免疫系统也会受到年龄的影响。免疫衰老的特征是免疫细胞在接触新抗原时产生有效反应的能力下降。多项研究报告称，长寿家族的成员显示出免疫功能改善，这可能有助于这些家族观察到的寿命和健康期延长。自噬是一种分解代谢过程，它将细胞质物质输送到溶酶体进行降解。已知自噬缺陷与多种细胞类型和组织的衰老有关，其失调与年龄相关疾病有关。在T细胞中，自噬在调节蛋白质和细胞器稳态以及激活诱导反应的调节中起重要作用。在本研究中，我们使用来自长寿家族的两个不同队列的个体，表明与年龄匹配的对照组相比，从长寿父母的后代中分离出的CD4+T细胞显示出改善的激活诱导自噬活性。有趣的是，自噬增加与干扰素-γ产生增加呈正相关。总之，自噬在长寿家族成员中似乎得到更好的维持，并且与改善的T细胞功能呈正相关。
