Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Laboratory of Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Aging Cell. 2021 Jan;20(1):e13283. doi: 10.1111/acel.13283. Epub 2020 Dec 23.
The mitochondrial free radical theory of aging suggests that accumulating oxidative damage to mitochondria and mitochondrial DNA (mtDNA) plays a central role in aging. Circulating cell-free mtDNA (ccf-mtDNA) isolated from blood may be a biomarker of disease. Extracellular vesicles (EVs) are small (30-400 nm), lipid-bound vesicles capable of shuttling proteins, nucleic acids, and lipids as part of intercellular communication systems. Here, we report that a portion of ccf-mtDNA in plasma is encapsulated in EVs. To address whether EV mtDNA levels change with human age, we analyzed mtDNA in EVs from individuals aged 30-64 years cross-sectionally and longitudinally. EV mtDNA levels decreased with age. Furthermore, the maximal mitochondrial respiration of cultured cells was differentially affected by EVs from old and young donors. Our results suggest that plasma mtDNA is present in EVs, that the level of EV-derived mtDNA is associated with age, and that EVs affect mitochondrial energetics in an EV age-dependent manner.
线粒体自由基衰老理论表明，线粒体和线粒体 DNA（mtDNA）的氧化损伤积累在衰老过程中起着核心作用。从血液中分离出的循环无细胞 mtDNA（ccf-mtDNA）可能是疾病的生物标志物。细胞外囊泡（EVs）是一种小的（30-400nm）、脂质结合的囊泡，能够作为细胞间通讯系统的一部分传递蛋白质、核酸和脂质。在这里，我们报告血浆中的一部分 ccf-mtDNA 被包裹在 EVs 中。为了研究 EV mtDNA 水平是否随人类年龄变化，我们对 30-64 岁个体的 EV 中的 mtDNA 进行了横断面和纵向分析。EV mtDNA 水平随年龄增长而降低。此外，来自老年和年轻供体的 EV 对培养细胞的最大线粒体呼吸产生了不同的影响。我们的结果表明，血浆 mtDNA 存在于 EVs 中，EV 衍生的 mtDNA 水平与年龄相关，并且 EV 以依赖 EV 年龄的方式影响线粒体能量代谢。
