Small extracellular vesicles improve health span and prevent frailty in old mice

Aging is associated with an increased risk of frailty, disability, and mortality. Strategies to delay the degenerative changes associated with aging and frailty are particularly interesting. University of Valencia researchers treated old animals with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and they found an improvement in several parameters usually altered with aging, such as motor coordination, grip strength, fatigue resistance, fur regeneration, and renal function, as well as an important decrease in frailty. ADSC-sEVs induced proregenerative effects and a decrease in oxidative stress, inflammation, and senescence markers in muscle and kidney. Moreover, predicted epigenetic age was lower in tissues of old mice treated with ADSC-sEVs and their metabolome changed to a youth-like pattern. Last, the researchers gained some insight into the microRNAs contained in sEVs that might be responsible for the observed effects. They propose that young sEV treatment can promote healthy aging.

ADSC-sEVs improve health span and prevent frailty in old mice

(A) Schematic representation of the experimental design. (B) Quantification of the change in total body weight; data are shown as the decrease in percentage from the baseline before treatment with sEVs/PBS. PBS: day 14, n = 12; day 30, n = 12; sEVs: day 14, n = 14; day 30, n = 15. (C to E) Quantification of the change in physical condition tests; data are shown as the change in percentage from baseline before treatment with sEVs/PBS. Grip strength: PBS: day 14, n = 11; day 30, n = 11; sEVs: day 14, n = 13; day 30, n = 11. Motor coordination: PBS: day 14, n = 14; day 30, n = 12; sEVs: day 14, n = 16; day 30, n = 18. Fatigue resistance: PBS: day 14, n = 12; day 30, n = 11; sEVs: day 14, n = 14; day 30, n = 15. (F) Quantification of the number of frail mice before and 30 days after treatment with sEVs/PBS, determined by a score based on the clinical phenotype of frailty. PBS: day 0, n = 12; day 30 n = 12; sEVs: day 0, n = 15; day 30, n = 15. (G) Quantification of the hair regrowth capacity of dorsal skin in old mice. PBS, n = 7; sEVs, n = 7. a.u., arbitrary units. (H) Representative image of hair regeneration in both male and female mice before and 14 days after treatment with sEVs/PBS. (I) Quantification of the changes in plasmatic urea; data are shown as the change in percentage from basal levels of urea in plasma before treatment with sEVs/PBS. PBS: day 14, n = 5; day 30, n = 4; sEVs: day 14, n = 5; day 30, n = 6. All data are shown as means ± SD.