Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for " inflamm- aging"
Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for " inflamm- aging"
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DOI：
10.1002/eji.201343921
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发表时间：
2014-05-01
影响因子：
5.4
通讯作者：
Cossarizza, Andrea
中科院分区：
文献类型：
--
作者：
Pinti, Marcello;Cevenini, Elisa;Cossarizza, Andrea
线粒体组分，包括线粒体DNA（mtDNA），当在细胞外释放时，可以充当损伤相关分子模式（DAMP）剂并引起炎症。由于许多老年人的特征是低级别的慢性炎症状态，定义为炎症老化，我们评估了循环mtDNA是否有助于这种现象。831例白人受试者入组本研究，包括429名90-104岁的兄弟姐妹（90+兄弟姐妹）。mtDNA血浆水平在50岁以后逐渐升高。在90多名受试者中，同一兄弟姐妹关系的两名成员的mtDNA值直接相关，这表明熟悉/遗传背景在控制循环mtDNA水平方面的作用。具有最高mtDNA血浆水平的受试者具有最高量的TNF-、IL-6、RANTES和IL-1 ra;具有最低mtDNA水平的受试者具有最低水平的相同细胞因子。在体外刺激单核细胞的mtDNA浓度类似于在体内观察到的最高水平，导致TNF-α的产生增加，这表明mtDNA可以调节促炎细胞因子的产生。因此，我们的研究结果表明，循环mtDNA随着年龄的增长而增加，并且可以显着促进老年人中观察到的低度慢性炎症的维持。
Mitochondrial components, including mitochondrial DNA (mtDNA), when released extracellularly, can act as damage-associated molecular pattern (DAMP) agents and cause inflammation. As many elderly people are characterized by a low-grade, chronic inflammatory status defined inflamm-aging, we evaluated if circulating mtDNA can contribute to this phenomenon. Eight hundred and thirty-one Caucasian subjects were enrolled in the study, including 429 siblings aged 90-104 (90+ siblings). mtDNA plasma levels increased gradually after the fifth decade of life. In 90+ subjects, mtDNA values of two members of the same sibling relationship were directly correlated, suggesting a role for familiar/genetic background in controlling the levels of circulating mtDNA. The subjects with the highest mtDNA plasma levels had the highest amounts of TNF-, IL-6, RANTES, and IL-1ra; the subjects with the lowest mtDNA levels had the lowest levels of the same cytokines. In vitro stimulation of monocytes with mtDNA concentrations similar to the highest levels observed in vivo resulted in an increased production of TNF-, suggesting that mtDNA can modulate the production of proinflammatory cytokines. Our findings therefore show that circulating mtDNA increases with age, and can significantly contribute to the maintenance of the low-grade, chronic inflammation observed in elderly people.