Dysregulation of miR144 and miR451 Expression in the Circulating Human Erythrocytes from the African American Adults

Abstract

There are several mechanisms that drive the aging process in the human body. Cellular senescence which leads to permanent cell growth arrest and oxidative stress are examples of aging promoting mechanisms. Moreover, genetics and epigenetic play important roles in accelerating and/or delaying the onset of the aging process. miRNAs are important players in controlling OS, aging, and cellular senescence. The purpose of this study was to evaluate circulating erythrocyte miR-451 and miR-144 expression as potential biomarker of cell aging. Blood samples were collected from consented volunteers and miRNAs were isolated from a control group and Type 2 Diabetes Mellitus. Taqman primers were used for detection and quantification of miR-144 and miR-451. Erythrocytes were further sub-fractionated into young, mid and old age by using discontinuous Percoll gradient. miRNA's were isolated from erythrocytes using miRNA Isolation kit. The miR-451 expression was significantly down-regulated in old cells in T2DM group, while miR-144 expression was significantly up-regulated in old cells in T2DM. The findings of this study are consistent with our previous report of increase expression of miR-451 and miR-144 as the cell gets old. The current findings suggest that miR-451 and miR-144 may have a role in aging process.

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

“…Targets SIRT1 and reduces its expression, leading to the activation of p53 and induction of cellular senescence [83] It is actively expressed in cardiac cells of aged mice, and inhibition or deletion reduces age-associated cardiomyocyte death [84] Increased expression in H2O2-induced premature cellular senescence [85] miR-21 ↑ Overexpression reduces the replicative lifespan of HUVECs [86] miR-146a miR-106a ↓ Five models of cellular senescence show reduced expression [92] miR-17-92 ↓ Increased expression in primary human fibroblasts inhibits Ras-induced cellular senescence [97] miR-15a ↓ Involved in the regulation of stress-induced senescence of WI-38 cells [96] miR-144 ↑ Increased expression in aged erythrocytes from type 2 diabetic patients [98] miR-494 ↑ Overexpression enhances DNA damage and cellular senescence in IMR90 cells [82] miR-449a ↓ Increased expression slows senescence in HUVECs and adipose tissue by targeting p16 Ink4a , p21 CIP1 , and the PI3K-mTOR signaling pathway [99] miR-17 ↓ All seven models of cellular senescence show reduced expression [92] miR-25 ↓ Downregulation in Ras-induced senescent WI-38 cells [96] miR-431 ↑ Increased expression in both replicative and stress-induced senescent human lung fibroblasts [96] miR-34a, a key regulator of SIRT1, is one of the major miRNAs involved in cellular senescence [83]. A positive feedback loop exists between miR-34a, SIRT1, and p53 where p53 activates miR-34a expression, which targets and represses SIRT1, preventing SIRT1mediated deacetylation of p53, thus promoting p53 activity [80].…”