Circulating factors play crucial roles in regulating tissue balance and regeneration. One approach used to identify the effects of these circulating factors on target tissues involves the surgical joining of a young and old mouse. This procedure enables heterochronic blood exchange — the coupling of circulatory systems from two animals, which exposes the aged mouse to circulatory factors from the young mouse and vice versa. This model has provided valuable insight into the influence of age-associated factors on the function of stem cells and tissues, including skeletal muscle.
Most studies investigating the beneficial effect of heterochronic parabiosis on aged tissue function have primarily focused on free circulating proteins. But a growing number of findings have demonstrated that many biomolecules secreted by cells are packaged within EVs, which traffic between anatomically remote sites and serve as couriers of proteins and genetic material. EVs have been identified in most bodily fluids, including plasma, serum, urine, saliva, and cerebrospinal fluid. Emerging evidence suggests that mRNA cargoes within EVs can target and reprogram cells in various tissues to regulate function.
Given their potent role in intercellular communication, it is not surprising that age-related alterations in the EVs and their cargo have been increasingly associated with age-related diseases. However, whether circulating EVs mediate the ‘rejuvenating’ effects of young blood on skeletal muscle regeneration in old mice has not been investigated. “We wondered if extracellular vesicles might contribute to muscle regeneration because these couriers travel between cells via the blood and other bodily fluids,” said lead author Amrita Sahu, Ph.D., a postdoctoral fellow in the Department of Physical Medicine and Rehabilitation at Pitt. “Like a message in a bottle, EVs deliver information to target cells.”