Liver cell patterns shifted with age and insulin resistance in mice
In five 20-month-old male mice, two weeks of a signaling protein reversed one liver-cell shift and improved insulin sensitivity compared with five controls.
Limit: Gene-defined zones could reflect changed cell identity or location rather than cell loss
Edited by Boris Djordjevic · AgingResearch.News
In experiments in male mice aged 3 or 20 months, researchers mapped liver cell types and locations. They analyzed cells from six mice: two young and insulin-sensitive, two old with mild insulin resistance, and two old with severe insulin resistance. Tissue maps came from six other mice.
Older mice had a smaller share of hepatocytes—the liver’s main cells—in zone 3, near central veins, and a larger share in the middle zone. Insulin resistance accompanied further shifts. Analyses pointed to reduced signaling from liver support cells to zone 3 cells through hepatocyte growth factor, a signaling protein. Five insulin-resistant, 20-month-old males received daily injections of this protein at 0.5 micrograms per kilogram for two weeks. Compared with five vehicle-injected controls, it reversed zone 3 contraction and improved their response to insulin.
Why it matters
Understanding how liver cell organization changes with age may help address why the body becomes less responsive to insulin, the hormone that controls blood sugar.
Caveats
The liver zones were defined by gene activity, so their shifts could reflect changed cell identity or location rather than cell loss. The experiments were small and involved only male mice.
The paper
University of California, Irvine
Metabolism, May 9, 2026
