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Mitochondrial DNA in extracellular vesicles declines with age

Stephanie Lazo1, Nicole Noren Hooten1, Jamal Green1

  • 1Laboratory of Epidemiology and Population Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Aging Cell
|December 28, 2020
PubMed

Insights

Levels of mitochondrial DNA (mtDNA) within extracellular vesicles (EVs) decrease with age. These age-associated EVs also impact cellular mitochondrial respiration, suggesting EVs are involved in aging processes.

Area of Science:

  • Gerontology
  • Mitochondrial Biology
  • Cellular Aging

Background:

  • The mitochondrial free radical theory of aging highlights oxidative damage to mitochondria and mitochondrial DNA (mtDNA) as a key aging factor.
  • Circulating cell-free mtDNA (ccf-mtDNA) in blood shows potential as a disease biomarker.
  • Extracellular vesicles (EVs) are crucial for intercellular communication, transporting various biomolecules.

Purpose of the Study:

  • To investigate if extracellular vesicle (EV)-encapsulated mtDNA levels change with human age.
  • To determine the impact of age-associated EVs on cellular mitochondrial function.

Main Methods:

  • Analysis of mtDNA within plasma-derived EVs from individuals aged 30-64 years.
  • Cross-sectional and longitudinal study designs.
  • Assessment of maximal mitochondrial respiration in cultured cells exposed to EVs from young and old donors.

Main Results:

  • Plasma mtDNA is significantly encapsulated within EVs.
  • EV-encapsulated mtDNA levels demonstrate a decrease with increasing age.
  • EVs from older donors differentially affected cellular mitochondrial respiration compared to EVs from younger donors.

Conclusions:

  • Plasma mtDNA is packaged within EVs, and EV-derived mtDNA levels correlate with age.
  • EVs influence mitochondrial energetics in an age-dependent manner.
  • EVs may play a role in age-related changes in mitochondrial function.
Keywords:
agingbiomarkercirculating cell-free mitochondrial DNAexosomesextracellular vesiclesintercellular communicationmicrovesiclesmitochondrial DNA

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