Extracellular Vesicles in Aging
Extracellular vesicles of varying size classes carry a sizable fraction of all cell signaling. These are membrane-wrapped collections of molecules, generated in various ways and under various circumstances by sources cells. When researchers discuss extracellular vesicles in the context of aging, this is really a discussion of cell signaling in general. In the context of aging, vesicles are perhaps a more interesting topic than cell signaling in general because they are readily harvested and delivered as a therapy. Initially, this is being used to recapitulate the effects of stem cell transplants, delivering vesicles harvested from stem cells in culture, but it is likely that there will be further, more engineered and specific vesicle-based therapies in the future.
In recent decades, the concept of extracellular vesicles (EVs) has changed. When they were initially discovered, EVs were cellular dust; therefore, they did not have any functions; with time, this concept has changed and will probably continue being updated. Nowadays, EVs are considered critical mediators in physiological and pathophysiological processes. Therefore, this review summarizes the current knowledge on EVs from their discovery as cellular dust to their recognition as "very important particles" (VIPs) that mediate cell-cell communication and the current and newest isolation methods. Moreover, we describe the role of EVs in aging and age-related diseases and their potential use in the clinic as biomarkers for early diagnosis and as therapeutic agents for disease treatment.
EVs display several features that provide them with invaluable abilities for their application in regenerative medicine. First, the EV content mimics their parental cells. Thus, isolation of EVs from body fluids with a specific cargo is very useful as a biomarker in disease development for early diagnosis. Second, EVs have a specific set of surface proteins that indicates their target cells. This characteristic also has a valuable potential for their use as drug-delivery carriers to target cells. To date, EVs are VIPs because they act as mediators in physiological and pathological processes. Particularly, as shown in this review, EVs mediate biological aging and premature aging by their content and number released by senescent cells.
Research is still needed in the EV therapeutic field, in particular, focusing on the development of autologous EVs that would enable personalized treatment for each specific disease. Regarding the research on EV-mediated mechanisms of aging, efforts should be performed to establish a time- and cargo-dependent correlation between EVs and the incidence of age-related diseases so that EVs become a very early biomarker. It is also necessary to elucidate the exact molecular mechanisms involved in the change in EV content during aging; this understanding would help us to develop new cell-free treatments to reverse age-related diseases in the future. However, it should be mentioned that before starting antiaging therapies with EVs, safety, sensitivity, and specificity must be precisely verified. Additionally, administration, dosages, treatment intervals, and duration must be strictly certified.