肥胖人群的T细胞产生的一种独特的炎症特征是二甲双胍抗性

IF 5.3 2区 医学 Q1 GERIATRICS & GERONTOLOGY GeroScience Pub Date : 2024-12-21 DOI:10.1007/s11357-024-01441-4
S. SantaCruz-Calvo, S. Saraswat, G. H. Kalantar, E. Zukowski, H. Marszalkowski, A. Javidan, F. Gholamrezaeinejad, L. P. Bharath, P. A. Kern, X. D. Zhang, B. S. Nikolajczyk
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引用次数: 0

摘要

老年人肥胖的患病率高得惊人,再加上肥胖和衰老过程中慢性炎症对健康的负面影响,这凸显了研究肥胖对年龄相关炎症影响的重要性。由于外周t细胞代谢和功能的变化驱动肥胖和衰老的全身性炎症,我们假设肥胖影响了我们在瘦受试者中发现的th17主导的炎症特征,从而改变了二甲双胍等老年保护药物的抗炎作用。新的细胞因子谱数据显示,老年肥胖患者的CD4+ T细胞产生了一种特异性排除Th17细胞因子的谱。二甲双胍未能改变肥胖中与年龄相关的t细胞谱,尽管降低了线粒体呼吸和活性氧(ROS)的产生。二甲双胍不能改善老年肥胖患者T细胞的巨噬,这与二甲双胍促进老年瘦人T细胞自噬的能力形成鲜明对比。这些数据表明,体重指数改变了老年受试者T细胞中支持炎症的机制,二甲双胍介导的氧化还原平衡恢复不足以阻止肥胖相关的炎症。我们得出结论,肥胖从根本上改变了促进炎症的机制,因此肥胖成为二甲双胍等老年保护剂临床试验的关键考虑因素。
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A unique inflammaging profile generated by T cells from people with obesity is metformin resistant

The alarmingly high prevalence of obesity in older adults coupled with the negative health effects of chronic inflammation in both obesity and aging highlight the importance of studies investigating the impacts of obesity on age-related inflammation. Since shifts in peripheral T-cell metabolism and function drive systemic inflammation in both obesity and aging, we hypothesize that obesity impacts the Th17-dominated inflammaging profile we identified in lean subjects and thus modifies the anti-inflammatory effects of geroprotective drugs like metformin. New cytokine profiling data showed that CD4+ T cells from older people with obesity generate a profile that specifically excludes Th17 cytokines. Metformin failed to change the age-associated T-cell profile in obesity, despite lowering both mitochondrial respiration and reactive oxygen species (ROS) production. Metformin did not improve macroautophagy in T cells from older people with obesity, in sharp contrast to the ability of metformin to promote autophagy in T cells from older lean subjects. These data indicate that body mass index modifies the mechanisms supporting inflammaging in T cells from older subjects, and that metformin-mediated restoration of redox balance is insufficient to stem obesity-associated inflammaging. We conclude that obesity fundamentally changes the mechanisms that promote inflammaging, and thus obesity becomes a critical consideration for clinical trials of geroprotective agents such as metformin.

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来源期刊
GeroScience
GeroScience Medicine-Complementary and Alternative Medicine
CiteScore
10.50
自引率
5.40%
发文量
182
期刊介绍: GeroScience is a bi-monthly, international, peer-reviewed journal that publishes articles related to research in the biology of aging and research on biomedical applications that impact aging. The scope of articles to be considered include evolutionary biology, biophysics, genetics, genomics, proteomics, molecular biology, cell biology, biochemistry, endocrinology, immunology, physiology, pharmacology, neuroscience, and psychology.
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