Aging is a process of cellular and tissue dysfunction characterized by different hallmarks, including cellular senescence. However, there is proof that certain features of aging and senescence can be ameliorated. Here, we provide evidence that small extracellular vesicles (sEVs) isolated from primary fibroblasts of young human donors ameliorate certain biomarkers of senescence in cells derived from old and Hutchinson-Gilford progeria syndrome donors. Importantly, sEVs from young cells ameliorate senescence in a variety of tissues in old mice. Mechanistically, we identified sEVs to have intrinsic glutathione-S-transferase activity partially due to the high levels of expression of the glutathione-related protein (GSTM2). Transfection of recombinant GSTM2 into sEVs derived from old fibroblasts restores their antioxidant capacity. sEVs increase the levels of reduced glutathione and decrease oxidative stress and lipid peroxidation both in vivo and in vitro. Altogether, our data provide an indication of the potential of sEVs as regenerative therapy in aging.

衰老是一个细胞和组织功能障碍的过程，具有不同的特征，包括细胞衰老。然而，有证据表明衰老和衰老的某些特征是可以改善的。在这里，我们提供的证据表明，从年轻人类供体的原代成纤维细胞中分离的小细胞外囊泡 (sEV) 改善了来自老年和 Hutchinson-Gilford 早衰综合征供体的细胞中衰老的某些生物标志物。重要的是，来自年轻细胞的 sEV 可改善老年小鼠各种组织的衰老。从机制上讲，我们发现 sEV 具有内在的谷胱甘肽-S-转移酶活性，部分原因是谷胱甘肽相关蛋白 (GSTM2) 的高水平表达。将重组 GSTM2 转染到来自旧成纤维细胞的 sEV 中可恢复其抗氧化能力。体内和体外。总而言之，我们的数据表明 sEV 作为衰老再生疗法的潜力。