Senescent cells accumulate in various tissues over time, and contribute to tissue dysfunction and aging-associated phenotypes. Accumulating evidence suggests that cellular senescence can be inhibited through pharmacological intervention, as well as through treatment with soluble factors derived from embryonic stem cells (ESCs). In an attempt to investigate the anti-senescence factors secreted by ESCs, we analyzed mouse ESC-derived extracellular miRNAs in conditioned medium (CM) via miRNA array analysis. We selected mmu-miR-291a-3p as a putative anti-senescence factor via bioinformatics analysis. We validated its inhibitory effects on replicative, adriamycin-induced, and ionizing radiation-induced senescence in human dermal fibroblasts. Treatment of senescent cells with mmu-miR-291a-3p decreased senescence-associated-β-galactosidase activity, enhanced proliferative potential, and reduced mRNA and protein expression of TGFBR2, p53, and p21. Mmu-miR-291a-3p in CM was enclosed in ESC-derived exosomes and exosomes purified from ESC-CM inhibited cellular senescence. The inhibitory effects of mmu-miR-291a-3p were mediated through the TGFBR2 signaling pathway. Hsa-miR-371a-3p and hsa-miR-520e, the human homologs of mmu-miR-291a-3p, showed similar anti-senescence activity. Furthermore, mmu-miR-291a-3p accelerated the excisional skin wound healing process in aged mice. Our results indicate that the ESC-derived mmu-miR-291a-3p is a novel candidate agent that can be utilized for cell-free therapeutic intervention against aging and aging-related diseases.

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Two unrecorded yeasts, Meyerozyma caribbica UL5-1 and Pichia silvicola UL6-1 were screened from 58 yeasts which were isolated from wild flowers in Ulleungdo in Gyeongsangbuk-do, Korea. The morphological and cultural characteristics of these unrecorded yeasts were investigated. Both yeasts were oval in shape and formed pseudomycelia. P. silvicola UL6-1 formed ascospore, but M. UL5-1 did not. P. silvicola UL6-1 and M. caribbica UL5-1 also grew in vitamin-free medium and 5% NaClcontaining yeast extract-peptone-dextrose medium. The two unrecorded yeasts assimilated glucose, galactose, xylose, cellobiose, trehalose, glycerol and sorbitol, and also fermented glucose, fructose and mannose. The supernatant of both M. caribbica UL5-1 and P. silvicola UL6-1 showed high antihypertensive angiotensin I-converting enzyme inhibitory activity of 84.2% and 82.6%, respectively. Cell-free extract of P. silvicola UL6-1 also showed very high anti-diabetic α-glucosidase inhibitory activity (85.8%).