Association of psychosocial stress and poverty with plasma and extracellular vesicle mitochondrial DNA levels

Perceived discrimination has been associated with poor age-related health outcomes, yet little is known about the molecular mechanisms. Previous data have indicated that exposure to acute psychological stress results in higher levels of circulating cell-free mitochondrial DNA (ccf-DNA) in blood. ccf-mtDNA is part of the damage-associated molecular pattern (DAMP) system where it can activate the innate immune system. The current study examined the relationship between perceived discrimination, race, and poverty with ccf-mtDNA in plasma and plasma-derived extracellular vesicles (EVs) in a cohort of African American and White men and women who experienced high or low perceived discrimination (N = 64). Ccf-mtDNA levels were quantified from plasma and plasma EVs. We found that among individuals living below poverty, those with higher perceived discrimination had lower ccf-mtDNA levels in both plasma and EVs than those with low perceived discrimination. With advancing age, ccf-mtDNA levels were higher in African American participants, while the opposite was observed in White participants. We also discovered that the EV inflammatory proteins IL-18 and Cystatin-D were associated with perceived discrimination and age, sex, or race. The presence of EV Caspase-8 and TNF were associated with perceived discrimination and poverty, while EV IL-8 and TNF and TWEAK were associated with perceived discrimination and sex. Our findings suggest that discrimination interacts with sex, race, and poverty to influence ccf-mtDNA levels in plasma and EVs and EV inflammatory proteins.