Meta-analysis of extracellular vesicles-associated protein abundance and aggregation during aging and disease in C....

Extracellular vesicles (EVs) contribute to the maintenance of organism-wide proteostasis by mediating intercellular communication. Loss of proteostasis and altered intercellular communication are associated with aging and age-related diseases, suggesting key roles for EVs. However, it is unclear how the proteome of the EVs changes with age. To identify EV-associated proteins (EVAPs) and their fate with age, we curated publicly available EV proteome data from C. elegans model organism and human. Our analysis reveals that EVs carry proteins with diverse functions, including those involved in protein quality control. We found that abundance of the EVAPs changes significantly with age, heat stress, pathogen infections and diseases. Many of these EVAPs also aggregate with age and overlap with Aβ-driven protein aggregates. Further, we identified human orthologs of C. elegans EVAPs from human brain tissues affected with Alzheimer's disease and breast cancer. This meta-analysis highlights EVs proteome composition, their abundance changes, and aggregation during aging, stress, infection and disease conditions. Overall, this study provides new insights into the dynamics of EV proteins during aging and may possibly help in identifying potential biomarkers for age-related diseases.