Much of the constant signaling that takes place between cells is carried via microvesicles and exosomes, membrane-bound packages of molecules. Researchers are finding that the contents of vesicles change in characteristic ways with advancing age, one of the many cellular reactions to rising levels of molecular damage and environmental stress. Some of these changes might be useful as a marker of cellular senescence, one of the more important changes in cell state associated with age. It should also be possible to use suitably formed vesicles to adjust cell behavior in situ, such as to spur greater regeneration. Perhaps these vesicles are harvested from young cells, or perhaps they might be manufactured directly. Many of the current class of widely used cell therapies might in theory be replaced by delivery of vesicles, as the cell therapies achieve their beneficial results via signaling, not other cell activities.

Another of the more important changes in cell state that occurs with age is the decline in stem cell activity. Stem cells are responsible for providing a supply of somatic cells for tissue maintenance and regeneration, and the progressive loss of that supply contributes to the gradual failure of tissue and organ function in later life. There is ample evidence to suggest that, at least in the stem cell populations most studied to date, such as those supporting skeletal muscle tissue, this is at least as much a problem of signaling as it is a problem of damage to the cells themselves. The stem cells react to the state of damage and behavior of other cells in the niche that supports them, as reflected in the signal molecules they receive. The current consensus in the scientific community is that this response to the damage of aging evolved to reduce cancer risk, one part of the current human life span as a balance between death by cancer versus death by slowly declining tissue function.

As research community interest in vesicle signaling picks up, we should expect to see more in the way of research results such as the one below, in which scientists find that delivery of vesicles from young niche cells can restore more youthful function to aged hematopoietic stem cells, the population resident in bone marrow and responsible for generating blood and immune cells. It seems plausible that we stand at the verge of an important shift in focus for the field of regenerative medicine, a change based on an improved understanding of how cells influence one another via signaling processes, and the identification of which of these signals are important determinants of the changes in regeneration and stem cell activity that occur over the course of aging.

Intercellular Transfer of Microvesicles from Young Mesenchymal Stromal Cells Rejuvenates Aged Murine Hematopoietic Stem Cells