%0 Journal Article
%T Blockade of senescenceİ\associated microRNAİ\195 in aged skeletal muscle cells facilitates reprogramming to produce induced pluripotent stem cells.
%A Christian Paul
%A Ha Won Kim
%A Hideyuki Kondo
%A Lei Wang
%A Motoi Okada
%A Ronald W. Millard
%A Yigang Wang
%J Archive of "Aging Cell".
%D 2016
%R 10.1111/acel.12411
%X The low reprogramming efficiency in cells from elderly patients is a challenge that must be overcome. Recently, it has been reported that senescenceİ\associated microRNA (miR)İ\195 targets Sirtuin 1 (SIRT1) to advance cellular senescence. Thus, we hypothesized that a blockade of miRİ\195 expression could improve reprogramming efficiency in old skeletal myoblasts (SkMs). We found that miRİ\195 expression was significantly higher in old SkMs (24 months) isolated from C57BL/6 mice as compared to young SkMs (2 months, 2.3İ\fold). Expression of SIRT1 and telomerase reverse transcriptase (TERT) was downregulated in old SkMs, and transduction of old SkMs with lentiviral miRİ\195 inhibitor significantly restored their expression. Furthermore, quantitative in situ hybridization analysis demonstrated significant telomere elongation in old SkMs transduced with antiİ\miRİ\195 (1.7İ\fold increase). It is important to note that blocking miRİ\195 expression markedly increased the reprogramming efficiency of old SkMs as compared to scramble (2.2İ\fold increase). Transduction of antiİ\miRİ\195 did not alter karyotype or pluripotency marker expression. Induced pluripotent stem cells (iPSCs) from old SkMs transduced with antiİ\miRİ\195 successfully formed embryoid bodies that spontaneously differentiated into three germ layers, indicating that deletion of miRİ\195 does not affect pluripotency in transformed SkMs. In conclusion, this study provided novel evidence that the blockade of ageİ\induced miRİ\195 is a promising approach for efficient iPSC generation from aging donor subjects, which has the potential for autologous transplantation of iPSCs in elderly patients
%K aging cell
%K microRNA
%K reprogramming
%K telomere length
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717278/