Functional characterization of miRNAs in aging of cells and organisms

Progressive functional decline of organ and tissue function contributes to the overall deterioration of organisms observed during aging. In order to dissect mechanisms underlying these functional changes, serial passaging until entry into replicative senescence of several different cell types like fibroblasts or endothelial cells has been used as model systems. Recently, we have established normal human renal proximal tubular epithelial cell lines (RPTECs) in vitro in order to study their physiological changes during in vitro aging and the underlying molecular mechanisms. These cells are lining the glomerular tubuli and are responsible for reabsorption of water, minerals, and protein of the renal filtrate. Changes of these cells during aging are of high medical interest, since aging associated changes of the kidney lead to decreased resistance against various stressors that can result in renal failure. In addition, several aging related diseases are caused or followed by nephropathies. Furthermore, senescent kidney cells have been observed to increase with age or, surprisingly, also with severity of graft rejection in transplantation patients. The novel class of post-transcriptional regulators, microRNAs (miRNAs), which control the stability and translation of specific target messenger RNAs, is of high interest, since it co-regulates the profile of protein expression. Up to now around 460 members of this novel “subgenome” have been identified in humans, however, the function of only few of these has been clarified so far, and no link to human cell aging has been established yet.