Frasca Daniela, Diaz Alain, Romero Maria, Blomberg Bonnie B
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, United States.
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, United States.
Front Aging. 2021 Jul 23;2:715981. doi: 10.3389/fragi.2021.715981. eCollection 2021.
Our previous work has shown that young and elderly patients with Type-2 Diabetes Mellitus (T2DM) treated with Metformin have optimal B cell function and serum antibodies specific for the seasonal influenza vaccine. In this paper, we have evaluated B cell function and the metabolic requirements of B cell antibody responses in elderly T2DM patients (E) taking or not Metformin, and compared to those of healthy elderly (E) and healthy young (Y) individuals. Results show that Metformin significantly increases B cell function, measured by influenza vaccine-specific serum antibodies, in E patients to the levels observed in E and more importantly in Y individuals. Metformin also decreases the frequencies of pro-inflammatory B cell subsets, as well as intrinsic inflammation and metabolic requirements of peripheral B cells from E. This hyper-metabolic phenotype of B cells from E is needed to support intrinsic inflammation, measured by the expression of transcripts for markers of the senescence-associated secretory phenotype (SASP), and the secretion of autoimmune antibodies. Importantly, B cell function in E patients taking Metformin is not only increased as compared to that in E patients not taking Metformin, but is comparable to B cell function measured in Y individuals. These results altogether strongly support the anti-aging effects of Metformin on humoral immunity.
我们之前的研究表明，接受二甲双胍治疗的2型糖尿病（T2DM）年轻和老年患者具有最佳的B细胞功能以及针对季节性流感疫苗的血清抗体。在本文中，我们评估了服用或未服用二甲双胍的老年T2DM患者（E组）的B细胞功能以及B细胞抗体应答的代谢需求，并与健康老年人（E组）和健康年轻人（Y组）进行了比较。结果显示，通过流感疫苗特异性血清抗体测量，二甲双胍可显著提高E组患者的B细胞功能，使其达到E组以及更重要的是Y组个体中观察到的水平。二甲双胍还降低了促炎B细胞亚群的频率，以及E组外周B细胞的内在炎症和代谢需求。E组B细胞的这种高代谢表型是支持通过衰老相关分泌表型（SASP）标志物转录本表达测量的内在炎症以及自身免疫抗体分泌所必需的。重要的是，服用二甲双胍的E组患者的B细胞功能不仅比未服用二甲双胍的E组患者有所增加，而且与Y组个体中测量的B细胞功能相当。这些结果共同有力地支持了二甲双胍对体液免疫的抗衰老作用。
