Inflammatory Proteins in Extracellular Vesicles Correlate with Mortality
Here, researchers demonstrate that inflammatory proteins found in extracellular vesicles, used by cells to communicate, are correlated with mortality risk. This is not a surprising result, as the signaling associated with chronic inflammation causes disruption of normal tissue function and cell behavior in many ways. It is an important contributing factor in the progression of age-related degeneration, and the risk of suffering many of the common age-related conditions is strongly correlated with the burden of chronic inflammation. Aiming to minimize age-related inflammation without disrupting immune function is a noteworthy goal for future research and development. Senolytic therapies to remove senescent cells and their pro-inflammatory signaling is a step forward, but other causes of age-related inflammation, such as the DNA debris released by stressed and dying cells, will be harder to deal with.
Even before the COVID-19 pandemic declines in life expectancy in the United States were attributed to increased mortality rates in midlife adults across racial and ethnic groups, indicating a need for markers to identify individuals at risk for early mortality. Extracellular vesicles (EVs) are small, lipid-bound vesicles capable of shuttling functional proteins, nucleic acids, and lipids. Given their role as intercellular communicators and potential biomarkers of disease, we explored whether circulating EVs may be markers of mortality in a prospective, racially, and socioeconomically diverse middle-aged cohort.
We isolated plasma EVs from 76 individuals (mean age = 59.6 years) who died within a 5 year period and 76 surviving individuals matched by age, race, and poverty status. There were no significant differences in EV concentration, size, or EV-associated mitochondrial DNA levels associated with mortality. We found that several EV-associated inflammatory proteins including CCL23, CSF-1, CXCL9, GDNF, MCP-1, STAMBP, and 4E-BP1 were significantly associated with mortality. IL-10RB and CDCP1 were more likely to be present in plasma EVs from deceased individuals than in their alive counterparts. Our results suggest that plasma EV-associated inflammatory proteins are promising potential clinical biomarkers of mortality.