Open AccessMitochondrial DNA in extracellular vesicles declines with age
Author(s) -
Lazo Stephanie,
Noren Hooten Nicole,
Green Jamal,
Eitan Erez,
Mode Nicolle A.,
Liu QingRong,
Zonderman Alan B.,
Ezike Ngozi,
Mattson Mark P.,
Ghosh Paritosh,
Evans Michele K.
Publication year - 2021
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13283
Subject(s) - mitochondrial dna , biology , mitochondrion , extracellular vesicles , nucleic acid , microbiology and biotechnology , oxidative phosphorylation , extracellular vesicle , genetics , microvesicles , biochemistry , gene , microrna
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.