Extracellular Vesicles from Young Mice Improve Health and Reduce Frailty in Old Mice
Much of cell signaling is carried via extracellular vesicles, membrane-wrapped packages of molecules. Researchers are finding that delivery of extracellular vesicles harvested from stem cells may be a good replacement for first generation stem cell therapies, in which the transplanted cells produce benefits via signaling before dying. Extracellular vesicles are an easier, cheaper approach from a logistical point of view. Here, researchers show that only vesicles generated by stem cells from young mice are capable of producing an impact on frailty in old mice, an indication of the degree to which aging impacts cell signaling and function.
Aging is associated with an increased risk of frailty, disability, comorbidities, institutionalization, falls, fractures, hospitalization, and mortality. Searching for strategies to delay the degenerative changes associated with aging and frailty is interesting. We treated old animals intravenously with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and we found an improvement of several functional parameters usually altered with aging, such as motor coordination, grip strength, fatigue resistance, fur regeneration, and renal function. Frailty index analysis showed that 40% of old control mice were frail, whereas none of the old ADSCs-sEVs treated mice were. Molecular and structural benefits in muscle and kidney accompanied this functional improvement.
ADSCs-sEVs induced pro-regenerative effects and a decrease in oxidative stress, inflammation, and senescence markers. The metabolome of treated mice changed to a youth-like pattern. Very interestingly, the effect of ADSCs-sEVs seems to be finite, as we observed in a more long-term experiment that the effect on the functionality of old mice was lost two months after treatment with ADSC-sEVs. Finally, we gained some insight into the miRNAs contained in sEVs that might be, at least in part, responsible for the effects observed. We propose that young sEVs treatment can be beneficial against frailty and therefore can promote healthy aging.