研究人员发现，由线粒体转录因子A（TFAM）缺乏引起线粒体功能异常的T细胞充当了衰老的加速器。
西班牙马德里12 de Octubre医院María Mittelbrunn小组取得一项新突破。他们发现线粒体功能异常的T细胞诱导多重病症和早衰。该项研究成果发表在2020年5月21日的《科学》上。
目前，尚不清楚免疫代谢对年龄有关疾病的影响。研究人员发现，由线粒体转录因子A（TFAM）缺乏引起线粒体功能异常的T细胞充当了衰老的加速器。在小鼠中，这些细胞会引发多种与衰老相关的特征，如代谢、认知、身体和心血管改变，这些共同导致过早死亡。
T细胞代谢衰竭导致循环细胞因子蓄积，这类似于衰老发生的慢性炎症（“发炎”）。这种细胞因子风暴本身可作为系统性衰老的诱导剂。用NAD +前体阻断TNF-α信号或预防衰老，可部分挽救T细胞Tfam缺陷小鼠的过早衰老。因此，T细胞可以调节机体适应性和寿命，这突显了严格的免疫代谢调控在衰老和年龄有关疾病发生中的重要性。
附：英文原文
Title: T cells with dysfunctional mitochondria induce multimorbidity and premature senescence
Author: Gabriela Desdín-Micó, Gonzalo Soto-Heredero, Juan Francisco Aranda, Jorge Oller, Elisa Carrasco, Enrique Gabandé-Rodríguez, Eva Maria Blanco, Arantzazu Alfranca, Lorena Cussó, Manuel Desco, Borja Ibaez, Arancha R. Gortazar, Pablo Fernández-Marcos, Maria N. Navarro, Bruno Hernaez, Antonio Alcamí, Francesc Baixauli, María Mittelbrunn
Issue&Volume: 2020/05/21
Abstract: Abstract The impact of immunometabolism on age-associated diseases remains uncertain. Here, we show that T cells with dysfunctional mitochondria due to mitochondrial transcription factor A (TFAM) deficiency act as accelerators of senescence. In mice, these cells instigate multiple aging-related features, including metabolic, cognitive, physical, and cardiovascular alterations, which together result in premature death. T cell metabolic failure induces the accumulation of circulating cytokines, which resembles chronic inflammation characteristic of aging (“inflammaging”). This cytokine storm itself acts as a systemic inducer of senescence. Blocking TNF-α signaling or preventing senescence with NAD+ precursors partially rescues premature aging in mice with Tfam-deficient T cells. Thus, T cells can regulate organismal fitness and lifespan, highlighting the importance of tight immunometabolic control in both aging and the onset of age-associated diseases.
DOI: 10.1126/science.aax0860
Source: https://science.sciencemag.org/content/early/2020/05/20/science.aax0860
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