Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Eur J Immunol. 2014 May;44(5):1552-62. doi: 10.1002/eji.201343921. Epub 2014 Feb 13.
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-α, 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-α, 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.
线粒体成分，包括线粒体 DNA（mtDNA），当释放到细胞外时，可以作为“损伤相关分子模式”（DAMP）物质引起炎症。由于许多老年人的特征是低度、慢性炎症状态，定义为“炎症衰老”，我们评估了循环 mtDNA 是否可以促成这种现象。831 名高加索受试者被纳入研究，包括 429 名年龄在 90-104 岁的兄弟姐妹（90+ 岁的兄弟姐妹）。mtDNA 血浆水平在 50 多岁后逐渐升高。在 90+ 岁的受试者中，同一对兄弟姐妹中两个成员的 mtDNA 值直接相关，表明家族/遗传背景在控制循环 mtDNA 水平方面起作用。mtDNA 血浆水平最高的受试者具有最高水平的 TNF-α、IL-6、RANTES 和 IL-1ra；mtDNA 水平最低的受试者具有最低水平的相同细胞因子。体外用类似于体内观察到的最高浓度的 mtDNA 刺激单核细胞，导致 TNF-α 的产生增加，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 随年龄增长而增加，并可显著促进老年人低度、慢性炎症的维持。
