Inflammaging? Blame T cells! Mitochondrial dysfunction in various tissues is a prominent characteristic of age-related deterioration, but it is unclear how mitochondrial dysfunction in particular cell types contributes to this process. Desdín-Micó et al. generated mice with T cells that were specifically deficient in a mitochondrial DNA–stabilizing protein. These animals exhibited multiple features associated with aging, including neurological, metabolic, muscular, and cardiovascular impairments. The defective T cells initiated an inflammatory program similar to that observed in older animals, a process called “inflammaging.” Blocking the cytokine tumor necrosis factor–α or administering precursors of the cofactor nicotinamide adenine dinucleotide restored many of these symptoms of senescence. These findings may potentially inform future therapies for age-associated diseases, as well as cachexia and cytokine-release syndrome. Science, this issue p. 1371 Mitochondrial stress in immunological T cells induces the symptoms of systemic aging. The effect of immunometabolism on age-associated diseases remains uncertain. In this work, we show that T cells with dysfunctional mitochondria owing 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 the chronic inflammation that is characteristic of aging (“inflammaging”). This cytokine storm itself acts as a systemic inducer of senescence. Blocking tumor necrosis factor–α signaling or preventing senescence with nicotinamide adenine dinucleotide precursors partially rescues premature aging in mice with Tfam-deficient T cells. Thus, T cells can regulate organismal fitness and life span, which highlights the importance of tight immunometabolic control in both aging and the onset of age-associated diseases.

中文翻译：

---

线粒体功能失调的 T 细胞诱导多发病和过早衰老

发炎？责备T细胞！各种组织中的线粒体功能障碍是与年龄相关的退化的一个突出特征，但尚不清楚特定细胞类型中的线粒体功能障碍如何促成这一过程。Desdín-Micó 等人。产生了 T 细胞特别缺乏线粒体 DNA 稳定蛋白的小鼠。这些动物表现出多种与衰老相关的特征，包括神经、代谢、肌肉和心血管损伤。有缺陷的 T 细胞启动了类似于在老年动物中观察到的炎症程序，这一过程称为“炎症”。阻断细胞因子肿瘤坏死因子-α 或给予辅助因子烟酰胺腺嘌呤二核苷酸的前体可以恢复许多衰老症状。这些发现可能会为年龄相关疾病以及恶病质和细胞因子释放综合征的未来治疗提供信息。科学，这个问题 p。1371 免疫性 T 细胞中的线粒体应激诱导全身性衰老的症状。免疫代谢对年龄相关疾病的影响仍不确定。在这项工作中，我们表明由于线粒体转录因子 A (TFAM) 缺乏导致线粒体功能障碍的 T 细胞充当衰老的加速器。在小鼠中，这些细胞会引发多种与衰老相关的特征，包括代谢、认知、身体和心血管的改变，共同导致过早死亡。T 细胞代谢衰竭会导致循环细胞因子的积累，这类似于衰老所特有的慢性炎症（“炎症”）。这种细胞因子风暴本身充当衰老的全身诱导剂。用烟酰胺腺嘌呤二核苷酸前体阻断肿瘤坏死因子-α 信号传导或防止衰老部分挽救了 Tfam 缺陷 T 细胞小鼠的过早衰老。因此，T 细胞可以调节机体健康和寿命，这突出了严格免疫代谢控制在衰老和年龄相关疾病发病中的重要性。