Unit of Infection Models, German Primate Center, Goettingen, Germany.
Department of Laboratory Animal Science, German Primate Center, Goettingen, Germany.
Am J Primatol. 2020 Jun;82(6):e23128. doi: 10.1002/ajp.23128. Epub 2020 Apr 4.
The social, health, and economic challenges of a steadily increasing aging population demand the use of appropriate translational animal models to address questions like healthy aging, vaccination strategies, or potential interventions during the aging process. Due to their genetic proximity to humans, especially nonhuman primates (NHPs) with a relatively short generation period compared to humans, qualify as excellent animal models for these purposes. The use of common marmosets (Callithrix jacchus) in gerontology research steadily increased over the last decades, yet important information about their aging parameters are still missing. We therefore aimed to characterize their aging immune system by comprehensive flow cytometric phenotyping of blood immune cells from juvenile, adult, aging, and geriatric animals. Aged and geriatric animals displayed clear signs of immunosenescence. A decline in CD4/CD8 ratio, increased expression of HLA-DR and PD-1, higher frequencies of CD95 memory cells, alterations in cytokine secretion, and a decline in the proliferative capacity proved T cell senescence in aging marmosets. Also, the B cell compartment was affected by age-related changes: while overall B cell numbers remained stable with advancing age, expression of the activation marker CD80 increased and immunoglobulin M expression decreased. Interestingly, marmoset B cell memory subset distribution rather mirrored the human situation than that of other NHP. CD21 CD27 naïve B cell frequencies decreased while those of CD21 CD27 tissue memory B cells increased with age. Furthermore, frequencies and numbers of NK cells as part of the innate immune system declined with advancing age. Thus, the observed immunological changes in common marmosets over their life span revealed several similarities to age-related changes in humans and encourages further studies to strengthen the common marmoset as a potential aging model.
人口老龄化的社会、健康和经济挑战需要使用适当的转化动物模型来解决诸如健康老龄化、疫苗接种策略或潜在的衰老过程干预等问题。由于它们与人类的遗传关系密切，尤其是与人类相比具有相对较短的世代周期的非人类灵长类动物（NHPs），非常适合作为这些目的的优秀动物模型。在过去几十年中，普通狨猴（Callithrix jacchus）在老年学研究中的使用稳步增加，但关于其衰老参数的重要信息仍然缺失。因此，我们旨在通过对幼年、成年、衰老和老年动物的血液免疫细胞进行全面流式细胞术表型分析来描述其衰老免疫系统。与年轻动物相比，老年和老年动物表现出明显的免疫衰老迹象。CD4/CD8 比值下降、HLA-DR 和 PD-1 表达增加、CD95 记忆细胞频率升高、细胞因子分泌改变以及增殖能力下降证明了衰老狨猴 T 细胞的衰老。此外，B 细胞群也受到年龄相关变化的影响：虽然随着年龄的增长，B 细胞总数保持稳定，但激活标志物 CD80 的表达增加，免疫球蛋白 M 的表达减少。有趣的是，狨猴 B 细胞记忆亚群的分布更类似于人类，而不是其他 NHP。随着年龄的增长，CD21 CD27 幼稚 B 细胞的频率下降，而 CD21 CD27 组织记忆 B 细胞的频率增加。此外，随着年龄的增长，作为先天免疫系统一部分的 NK 细胞的频率和数量也会下降。因此，在普通狨猴的整个生命过程中观察到的免疫变化与人类的年龄相关变化有几个相似之处，这鼓励进一步的研究来加强普通狨猴作为潜在的衰老模型。
