“Ploidy Conveyer” reverse aging on hepatocytes

It’s obvious that the better understanding of hepatocyte senescence could be used to treat age-dependent disease processes of the liver. But whether the continuously proliferating hepatocytes could avoid or reverse senescence has not been fully not elucidated yet. The scientists in the Second Military Medical Universy confirmed that the livers of aged mice accumulated senescent and polyploid hepatocytes, which is associated with accumulation of DNA damage and activation of p53-p21 and p16ink4a -pRB pathways. Induction of multiple rounds continuous cell division is hard to apply in any animal model. Taking advantage of serial hepatocyte transplantation assays in the fumarylacetoacetate hydrolase deficient (Fah-/- ) mouse, they studied the senescence of hepatocytes that had undergone continuous cell proliferation over a long time period, up to 12 rounds of serial transplantations.

Finally, they demonstrated that the continuously proliferating hepatocytes avoided senescence and always maintained a youthful state. The re-activation of telomerase in hepatocytes after serial transplantation correlated with reversal of senescence. Moreover, senescent hepatocytes harvested from aged mice became rejuvenated upon serial transplantation, with full restoration of proliferative capacity. The same findings were also true for human hepatocytes. After serial transplantation, the high initial proportion of octoploid hepatocytes decreased to match the low level of youthful liver, suggesting that the hepatocyte "ploidy conveyer" is regulated differently during aging and regeneration. Their findings of reversal of hepatocyte senescence could enable future studies on liver aging and cell therapy.

Amyloid precursor protein (APP) is a transmembrane glycoprotein proteolytically processed to release amyloid beta, a pathological hallmark of Alzheimer's disease. APP is expressed throughout the developing and mature brain. However, the primary function of this protein is unknown.

It’s demonstrated previously that APP deficiency enhances neurogenesis, but the mechanisms underlying this process are not known. The scientists showed that APP regulates the expression of microRNAs in the cortex and in neural progenitors, specifically repressing miR-574-5p. And they also showed that overexpression of miR-574-5p promotes neurogenesis, but reduces the neural progenitor pool. In contrast, the reduced expression of miR-574-5p inhibits neurogenesis and stimulates proliferation in vitro and in utero. Furthermore they demonstrated that the inhibition of miR-574-5p in APP-knockout mice rescues the phenotypes associated with APP deficiency in neurogenesis. Taken these together, their results reveal a mechanism in which APP regulates the neurogenesis through miRNA-mediated post-transcriptional regulation.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.