More on Extracellular Vesicles in Aging, and as a Treatment for Age-Related Conditions
The review paper here might be compared with a very similar paper noted a few days ago. Any discussion of extracellular vesicles is essentially a discussion of cell signaling in general. Extracellular vesicles are membrane wrapped packages of signaling molecules that carry a sizable fraction of all of the varied signaling molecules that pass between cells. Cell signaling changes with age because cell behavior changes with age, and thus this is a vast topic, and hard to do more than touch on summary points in a single paper. It is perhaps the case that more attention is being given to extracellular vesicles these days because they can be harvested from cell cultures and used in therapies. This initially offers a logistically less complicated alternative to stem cell transplants, but potentially more interesting and more engineered therapies in the future.
Extracellular vesicles (EVs) are membrane-enclosed particles secreted by cells and circulating in body fluids. Initially considered as a tool to dispose of unnecessary material, they are now considered an additional method to transmit cell signals. EV alteration with aging suggests that the modulation of EV release, in terms of number and content, could represent a target to slow aging and for the therapy of age-related diseases.
First, the evaluation of EV features associated with aging (i.e., number, size, specific markers, genetic and/or biochemical content) could represent a possible biomarker of aging, useful to evaluate a variety of age-delaying therapeutic approaches. Second, the decrease of EVs number, via the removal of senescent cells which are known to release a higher number of EVs, could represent a rejuvenating tool associated with treatment with senolytic drugs. Third, the administration of EVs including key components showing anti-aging effects could be an effective rejuvenating strategy, potentially safer than the administration of whole cells.
Nonetheless, these studies are still preliminary and key issues have still to be elucidated. These challenges require further studies assessing the specific content of aging-associated EVs, as well as the development of methods and tools to produce EVs containing rejuvenating factors in a safe and abundant manner. In cell models, there is agreement that cell senescence is associated with an increased release of EVs, but the functional role of these EVs is less clear, as a few studies have reported pro-senescent and pro-apoptotic effects, whereas others have described a pro-tumorigenic role.
As for body fluid EVs, further studies are needed to assess whether aging is associated with an increased or decreased number of EVs, and the main biochemical features of EVs circulating in old versus young individuals, both in humans and in animal models, need to be further elucidated. Indeed, it must be considered that these samples are subjected to mechanical, chemical, and thermal stress during sampling and processing. This may notably change the shape, size, and composition of EVs in a manner that could be possibly influenced by age-related factors. However, there is converging evidence that EVs from young subjects have a rejuvenating effect and vice versa.