Researchers at the Keck School of Medicine of USC found that an experimental drug called cinaciguat reversed aging in specialized liver cells in older rats. After two weeks of treatment, amyloid beta, a protein linked to Alzheimer's disease, dropped by approximately 50%, reaching levels seen in young rats. LDL cholesterol also fell to youthful levels. The findings appear in the Journal of Biological Chemistry.
The study focused on liver sinusoidal endothelial cells, which form the lining of tiny blood vessels in the liver. These cells contain microscopic openings that allow larger molecules in the blood to reach neighboring cells responsible for removing substances from the body. As the liver ages, these openings shrink or close, making it harder to clear harmful proteins from circulation.
Cinaciguat restored the structure and function of the aging cells by reopening their microscopic pores. The drug also activated an enzyme called soluble guanylate cyclase inside these cells, triggering them to release a growth factor called HB-EGF. This signaling prompted neighboring hepatocytes to capture more amyloid beta and LDL from the blood. The researchers discovered this previously unknown communication pathway between the two cell types.
"We need to do further translational work to see whether our findings might point to new therapies," said Laurie DeLeve, MD, PhD, corresponding author and professor at USC. "We're hopeful, though, because the findings line up with a lot of epidemiological results showing age as a major risk factor for Alzheimer's and atherosclerosis, and liver damage as a risk factor for Alzheimer's."
The researchers note that treatments targeting Alzheimer's directly in the brain have faced an estimated 98% failure rate in clinical trials due to the blood-brain barrier. Targeting the liver could bypass this obstacle. However, the results have only been demonstrated in rats, and additional studies are needed to test whether the same benefits occur in humans.