Experimental drug restores aging liver cells and halves Alzheimer protein in rats
The liver filters the blood and clears harmful proteins. But that function declines with age. Researchers have now shown in a rat model that an experimental drug can reverse key signs of liver aging, cutting levels of an Alzheimer-linked protein by half.
The liver contains specialised cells lining its tiny blood vessels. These liver sinusoidal endothelial cells (LSECs) are studded with microscopic pores that allow large molecules to leave the bloodstream and be broken down. As the liver ages, those pores shrink or disappear, leaving harmful substances in circulation for longer. One affected substance is amyloid-beta, a protein associated with Alzheimer’s disease.
Experimental drug restores liver pores in rats
Researchers at the Keck School of Medicine of USC administered the experimental drug cinaciguat to older rats for two weeks. The study was published in the Journal of Biological Chemistry. After treatment, blood concentrations of amyloid-beta fell by roughly 50%, reaching levels comparable to young rats. LDL cholesterol also dropped to youthful levels. This last finding surprised the researchers, since LDL particles are too small to leave the blood through LSEC pores.
A previously unknown signalling system
Further investigation revealed a previously unknown communication pathway. Cinaciguat activates an enzyme in the LSECs, causing them to release a growth factor that prompts neighbouring liver cells (hepatocytes) to take up more LDL and amyloid-beta. This system appears to break down with age, and the drug appeared to restore it. The researchers stress that these findings have so far been demonstrated only in rats, and further studies are needed to determine whether the same effects occur in humans.
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