Mitochondrial DNA in extracellular vesicles declines with age.

Mitochondrial DNA in extracellular vesicles declines with age.
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DOI:
10.1111/acel.13283
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发表时间:
2021-01
期刊:
影响因子:
7.8
通讯作者:
Evans MK
Evans MK
中科院分区:
生物学1区
文献类型:
--
作者:
Lazo S;Noren Hooten N;Green J;Eitan E;Mode NA;Liu QR;Zonderman AB;Ezike N;Mattson MP;Ghosh P;Evans MK

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衰老的线粒体自由基学说表明,线粒体和线粒体DNA(MtDNA)氧化损伤的积累在衰老中起着核心作用。从血液中分离的循环无细胞线粒体DNA(CCF-mtDNA)可能是疾病的生物标志物。细胞外小泡(EV)是一种小的(30-400 nm)脂质结合的小泡,作为细胞间通讯系统的一部分,能够穿梭蛋白质、核酸和脂质。在这里,我们报告了血浆中CCF-mtDNA的一部分被包裹在EVS中。为了解决EV mtDNA水平是否随年龄变化的问题,我们对30-年龄段的EV中的mtDNA进行了横截面和纵向分析。EV线粒体DNA水平随年龄增长而降低。此外,老年和年轻供者的EV对培养细胞的最大线粒体呼吸也有不同的影响。我们的结果提示EVS中存在血浆mtDNA,EV来源的mtDNA水平与年龄有关,EVS以EV年龄依赖的方式影响线粒体能量学。线粒体功能障碍在衰老过程中起着核心作用。从血液中分离出的一部分循环中的无细胞线粒体DNA(MtDNA)存在于细胞外小泡(EV)中,EV是一种小的、脂质结合的小泡,作为细胞间通讯系统的一部分运送大分子。EV来源的线粒体DNA水平随着年龄的增长而下降,这些EV以EV年龄依赖的方式影响线粒体能量学。
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. Mitochondrial dysfunction plays a central role in aging. A portion of circulating cell‐free mitochondrial DNA (mtDNA) isolated from blood is present in extracellular vesicles (EVs), which are small, lipid‐bound vesicles that shuttle macromolecules as part of intercellular communication systems. The level of EV‐derived mtDNA declines with age, and these EVs affect mitochondrial energetics in an EV age‐dependent manner.
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