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
Summary
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.
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