The effect of metformin on influenza vaccine responses in nondiabetic older adults: a pilot trial.
The effect of metformin on influenza vaccine responses in nondiabetic older adults: a pilot trial.
复制标题
DOI：
10.1186/s12979-023-00343-x
复制
发表时间：
2023-05-02
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
衰老与免疫反应的逐渐下降有关，导致严重感染的风险增加和疫苗接种反应减弱。尽管有季节性疫苗，流感仍是老年人的主要杀手。以生物衰老为目标的遗传科学指导干预可以提供变革性的方法来逆转随着年龄增长而出现的免疫反应的广泛下降。在此，我们在一项试点和可行性双盲安慰剂对照研究中评估了二甲双胍（FDA批准的糖尿病药物和候选抗衰老药物）对流感疫苗接种反应和免疫弹性标志物的影响。健康老年人（非糖尿病/非糖尿病前期，年龄：74.4±1.7岁）随机分为二甲双胍组（n = 8, 1500 mg缓释/天）或安慰剂组（n = 7），治疗20周，治疗10周后接种高剂量流感疫苗。在治疗前、接种前、接种后1周、5周和10周采集外周血单个核细胞（PBMCs）、血清和血浆。接种疫苗后血清抗体滴度升高，组间无显著差异。二甲双胍治疗导致接种后循环T滤泡辅助细胞呈上升趋势。此外，二甲双胍治疗20周可降低循环CD4 T细胞中衰竭标志物CD57的表达。在非糖尿病老年人中，接种二甲双胍前治疗改善了流感疫苗反应的某些成分，减少了T细胞耗竭的一些标志物，没有发生严重的不良事件。因此，我们的研究结果强调了二甲双胍在改善流感疫苗反应和减少老年人与年龄相关的免疫衰竭方面的潜在效用，为非糖尿病老年人提供了改善的免疫恢复能力。在线版本包含补充材料，可在10.1186/s12979-023-00343-x获得。
Aging is associated with progressive declines in immune responses leading to increased risk of severe infection and diminished vaccination responses. Influenza (flu) is a leading killer of older adults despite availability of seasonal vaccines. Geroscience-guided interventions targeting biological aging could offer transformational approaches to reverse broad declines in immune responses with aging. Here, we evaluated effects of metformin, an FDA approved diabetes drug and candidate anti-aging drug, on flu vaccination responses and markers of immunological resilience in a pilot and feasibility double-blinded placebo-controlled study. Healthy older adults (non-diabetic/non-prediabetic, age: 74.4 ± 1.7 years) were randomized to metformin (n = 8, 1500 mg extended release/daily) or placebo (n = 7) treatment for 20 weeks and were vaccinated with high-dose flu vaccine after 10 weeks of treatment. Peripheral blood mononuclear cells (PBMCs), serum, and plasma were collected prior to treatment, immediately prior to vaccination, and 1, 5, and 10 weeks post vaccination. Increased serum antibody titers were observed post vaccination with no significant differences between groups. Metformin treatment led to trending increases in circulating T follicular helper cells post-vaccination. Furthermore, 20 weeks of metformin treatment reduced expression of exhaustion marker CD57 in circulating CD4 T cells. Pre-vaccination metformin treatment improved some components of flu vaccine responses and reduced some markers of T cell exhaustion without serious adverse events in nondiabetic older adults. Thus, our findings highlight the potential utility of metformin to improve flu vaccine responses and reduce age-related immune exhaustion in older adults, providing improved immunological resilience in nondiabetic older adults. The online version contains supplementary material available at 10.1186/s12979-023-00343-x.
登录
查看更多内容
影响因子：
5.6
作者：
Chen, Zhilan;Wei, Huafang;Zhang, Qinghua
通讯作者：
Zhang, Qinghua
影响因子：
--
作者：
Frasca, Daniela;Diaz, Alain;Romero, Maria;Blomberg, Bonnie B.
通讯作者：
Blomberg, Bonnie B.
影响因子：
16.2
作者：
Cowie CC;Rust KF;Ford ES;Eberhardt MS;Byrd-Holt DD;Li C;Williams DE;Gregg EW;Bainbridge KE;Saydah SH;Geiss LS
通讯作者：
Geiss LS
DOI：
10.1038/nri3198
发表时间：
2012-04-20
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
二甲双胍对小鼠脂肪衍生的多能基质细胞和脂肪组织中骨桥蛋白表达的体外和体内作用。
影响因子：
4.3
作者：
Śmieszek A;Basińska K;Chrząstek K;Marycz K
通讯作者：
Marycz K