Small extracellular vesicles from young adipose-derived stem cells prevent frailty, improve health span, and decrease epigenetic age in old mice

• DOI: 10.1126/sciadv.abq2226
• Publication Date: 2022-10-19T17:57:23Z
• Authors: Jorge Sanz-Ros; Nekane Romero-García; Cristina Mas-Bargues; Daniel Monleón; Juozas Gordevicius; Robert T. Brooke; Mar Dromant; Ana Díaz; Aksinya Derevyanko; Ana Guío-Carrión; Aurora Román-Domí...; Marta Inglés; María A. Blasco; Steve Horvath; Jose Viña; Consuelo Borrás
• Keywords: 0301 basic medicine; 03 medical and health sciences; Mortalitat; Biomedicine and Life Sciences; Discapacitat física; Persones grans; 3. Good health

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. We treated old animals with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and we 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, we gained some insight into the microRNAs contained in sEVs that might be responsible for the observed effects. We propose that young sEV treatment can promote healthy aging.