Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Division of Immunology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA.
J Leukoc Biol. 2021 Jun;109(6):1033-1043. doi: 10.1002/JLB.1HI1120-779R. Epub 2021 May 11.
Aging is characterized by a loss of bone marrow hematopoietic tissue, systemic chronic inflammation, and higher susceptibility to infectious and noninfectious diseases. We previously reported the tightly regulated kinetics and massive daily production of neutrophils during homeostasis in adult rhesus macaques aged 3 to 19 yr (equivalent to approximately 10 to 70 yr of age in humans). In the current study, we observed an earlier release of recently dividing neutrophils from bone marrow and greater in-group variability of neutrophil kinetics based on in vivo BrdU labeling in a group of older rhesus macaques of 20-26 yr of age. Comparing neutrophil numbers and circulating cytokine levels in rhesus macaques spanning 2 to 26 yr of age, we found a negative correlation between age and blood neutrophil counts and a positive correlation between age and plasma G-CSF levels. Hierarchic clustering analysis also identified strong associations between G-CSF with the proinflammatory cytokines, IL-1β and MIP-1α. Furthermore, neutrophils from older macaques expressed less myeloperoxidase and comprised higher frequencies of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) compared to the young adult macaques. In summary, we observed an earlier release from bone marrow and a reduced production of neutrophils despite the increased levels of plasma G-CSF, especially in the elderly rhesus macaques. This lower neutrophil production capacity associated with increased production of proinflammatory cytokines as well as an earlier release of less mature neutrophils and PMN-MDSCs may contribute to the chronic inflammation and greater susceptibility to infectious and noninfectious diseases during aging.
衰老是指骨髓造血组织的丧失、全身性慢性炎症以及对感染性和非感染性疾病的易感性增加。我们之前报道过，在 3 至 19 岁（相当于人类的 10 至 70 岁）的成年恒河猴中，中性粒细胞在稳态下有着严格调控的动力学和大量的日常产生。在当前的研究中，我们观察到在一组年龄较大的 20 至 26 岁的恒河猴中，最近分裂的中性粒细胞更早地从骨髓中释放出来，并且中性粒细胞动力学的个体内变异性更大，这是基于体内 BrdU 标记。比较 2 至 26 岁恒河猴的中性粒细胞数量和循环细胞因子水平，我们发现年龄与血液中性粒细胞计数呈负相关，与血浆 G-CSF 水平呈正相关。层次聚类分析还发现 G-CSF 与促炎细胞因子 IL-1β 和 MIP-1α 之间存在很强的关联。此外，与年轻成年猕猴相比，老年猕猴的中性粒细胞表达的髓过氧化物酶较少，并且多形核髓源性抑制细胞（PMN-MDSC）的频率更高。总之，我们观察到中性粒细胞更早地从骨髓中释放出来，并且尽管血浆 G-CSF 水平增加，但中性粒细胞的产生减少，尤其是在老年恒河猴中。这种较低的中性粒细胞产生能力与促炎细胞因子的产生增加以及更早释放不成熟的中性粒细胞和 PMN-MDSC 有关，可能导致衰老过程中的慢性炎症和对感染性和非感染性疾病的易感性增加。
