Young serum-derived exosomes potentially attenuate inflammaging via partially rejuvenating immuotolerance (Supported by NIH/NIAID R01AI121147 to D-M. S.)

Abstract Aging results in a chronic inflammatory condition, termed inflammaging, establishing a risk for age-related, such as neurocardiovascular, diseases. Therefore, it is of great importance to develop rejuvenating strategies able to attenuate inflammaging as a means to help intervention of age-related diseases. A promising “rejuvenation factor” present in young blood has been found to be able to make aged neuron “younger”. However, the component in the young serum is largely unclear. Herein, we tested rejuvenation in naturally-aged mice with a potential factor – young serum-derived exosomes, based on different spectrums of microRNAs in the young and old exosomes. We found that young murine serum-derived exosomes were able to attenuate inflammaging in both the periphery and the central nerve system of old mice. In addition to senescent cells secreting pro-inflammatory factors, thymic aging-released self-reactive T cell-induced autoimmune predisposition is another potential etiology of inflammaging, we identified that the young serum-derived exosome-attenuating inflammaging was partially attributed to rejuvenation of thymic aging, characterized by reversed thymic involution and improved function in negative selection. Our pilot work provides a clue of the rejuvenation factor in the young serum, which holds great promise toward the development of novel therapeutics to reduce morbidity and mortality caused by age-related diseases.