T cells with dysfunctional mitochondria induce multimorbidity and premature senescence

doi:10.1126/science.aax0860

GSTDTAP > 气候变化

DOI	10.1126/science.aax0860
	T cells with dysfunctional mitochondria induce multimorbidity and premature senescence
	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 Ibañez; Arancha R. Gortazar; Pablo Fernández-Marcos; Maria N. Navarro; Bruno Hernaez; Antonio Alcamí; Francesc Baixauli; María Mittelbrunn
	2020-06-19
发表期刊	Science
出版年	2020
英文摘要	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][1] 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. [1]: /lookup/doi/10.1126/science.aax0860
领域	气候变化 ; 资源环境
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/276700
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Gabriela Desdín-Micó,Gonzalo Soto-Heredero,Juan Francisco Aranda,et al. T cells with dysfunctional mitochondria induce multimorbidity and premature senescence[J]. Science,2020.
APA	Gabriela Desdín-Micó.,Gonzalo Soto-Heredero.,Juan Francisco Aranda.,Jorge Oller.,Elisa Carrasco.,...&María Mittelbrunn.(2020).T cells with dysfunctional mitochondria induce multimorbidity and premature senescence.Science.
MLA	Gabriela Desdín-Micó,et al."T cells with dysfunctional mitochondria induce multimorbidity and premature senescence".Science (2020).