Young Human Plasma Rejuvenates Senescent Vascular Endothelial Cell through Multiple Pathways

A mouse parabiotic model supports the existence of transferable factor(s) in blood that rescue(s) age-related degenerative phenotypes, however, whether it prevents endothelial cell senescence linked to common cardio-cerebral vascular diseases, requires to be inspected. In this study, plasmas donated from 27 young (23.04 ± 4.86 years, young human plasma, YHP) and 26 elderly (55.04 ± 5.42 years, elderly human plasma, EHP) healthy volunteers were used to culture primary human umbilical endothelial cells (HUVEC). When comparing with EHP, we found that the YHP reduced the percentages of SABG-stained cells and prohibited the expressions of senescent markers, including p16, p21, and p53 in HUVEC. Functionally, the YHP decreased the expression of ICAM-1, a marker for endothelial cell activation and increased abilities in tube formation and mobility at late passages that represent an enhanced angiogenic function. Validated by both RNA sequencing and Real-time PCR in HUVECs from all three umbilical cords, nineteen up-regulated and fifteen down-regulated genes were observed in YHP-treated HUVEC compared with group treated with the EHP. Among 34 genes, the expressions of MCM10, DHCR24, WBP1, UNC5B, and CYP26B1 were reversed by the YHP and we showed that these reversed expressions delayed senescence of both HUVEC and human coronary artery endothelial cell (HCAEC) through p16- and/or p21-assocated signaling. The five genes are relevant to maintain or reinstate the ability for proliferation, anti-apoptosis, and endothelial cell related functions, such as angiogenesis and anti-atherosclerosis. Thus, our study suggests that YHP restores biological processes in senescent endothelial cell through multiple pathways. Validated by both RNA sequencing and Real-time PCR in HUVECs from all three umbilical cords, nineteen up-regulated and fifteen down-regulated genes were observed in YHP-treated HUVEC compared with group treated with the EHP