炎症
Uniporter公司
线粒体
细胞生物学
胞浆
转录组
钙
生物
钙信号传导
蛋白质亚单位
信号转导
免疫学
基因
基因表达
医学
生物化学
内科学
酶
作者
Philip V. Seegren,Logan R. Harper,Taylor K. Downs,Xiaoyu Zhao,Shivapriya B. Viswanathan,Marta E. Stremska,Rachel J. Olson,Joel Kennedy,Sarah E. Ewald,Pankaj Kumar,Bimal N. Desai
出处
期刊:Nature Aging
日期:2023-06-05
卷期号:3 (7): 796-812
被引量:17
标识
DOI:10.1038/s43587-023-00436-8
摘要
Mitochondrial dysfunction is linked to age-associated inflammation or inflammaging, but underlying mechanisms are not understood. Analyses of 700 human blood transcriptomes revealed clear signs of age-associated low-grade inflammation. Among changes in mitochondrial components, we found that the expression of mitochondrial calcium uniporter (MCU) and its regulatory subunit MICU1, genes central to mitochondrial Ca2+ (mCa2+) signaling, correlated inversely with age. Indeed, mCa2+ uptake capacity of mouse macrophages decreased significantly with age. We show that in both human and mouse macrophages, reduced mCa2+ uptake amplifies cytosolic Ca2+ oscillations and potentiates downstream nuclear factor kappa B activation, which is central to inflammation. Our findings pinpoint the mitochondrial calcium uniporter complex as a keystone molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation. The findings raise the exciting possibility that restoring mCa2+ uptake capacity in tissue-resident macrophages may decrease inflammaging of specific organs and alleviate age-associated conditions such as neurodegenerative and cardiometabolic diseases.
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