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Abstract
Induced pluripotent stem cells (iPSCs) derived through somatic cell reprogramming have been reported to reset aged somatic cells to a more youthful state, characterized by elongated telomeres, a rearranged mitochondrial network, reduced oxidative stress and restored pluripotency. However, it is still unclear whether the reprogrammed aged somatic cells can function normally as embryonic stem cells (ESCs) during development and be rejuvenated. In the current study, we applied the aggregation technique to investigate whether iPSCs derived from aged somatic cells could develop normally and be rejuvenated. iPSCs derived from bone marrow myeloid cells of 2-month-old (2M) and 18-month-old (18M) C57BL/6-Tg (CAG-EGFP)1Osb/J mice were aggregated with embryos derived from wild-type ICR mice to produce chimeras (referred to as 2M CA and 18M CA, respectively). Our observations focused on whether the iPSCs derived from 18M bone marrow cells could develop rejuvenated cardiac tissue (the heart is the most vital organ during aging) compared with 2M bone marrow cells. The results showed an absence of p16 and p53 upregulation, telomere length shortening and mitochondrial genes expressions and deletions in 18M CA, while slight changes in mitochondria ultrastructure, cytochrome C oxidase activity,ATP production and reactive oxygen species (ROS) production were observed in CA cardiac tissues. The data implied that all of the aging characteristics observed in the newborn cardiac tissue of 18M CA was comparable with those of 2M CA newborn cardiac tissue.
FOR THE FIRST TIME, DIRECT EVIDENCE OF THE AGING-RELATED CHARACTERISTICS OF CARDIAC TISSUE DEVELOPED FROM AGED IPSCS IS PROVIDED, AND OUR OBSERVATIONS DEMONSTRATE THAT PARTIAL REJUVENATION CAN BE ACHIEVED BY REPROGRAMMING AGED SOMATIC CELLS TO A PLURIPOTENT STATE.
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http://online.lieber...9/rej.2017.1930
