PD-L2 blockade reduces aging-cell buildup in mice

Cedars-Sinai-led researchers identified PD-L2 as one protein that may help senescent aging cells avoid immune clearance, according to a peer-reviewed Cell Metabolism study published Oct. 14.

Evidence grade: Early (small, animal, cell or preprint). The work mainly involved laboratory mice, human cells and human tissues; the release did not provide sample sizes or absolute effect sizes.

Senescent cells are damaged or aged cells that stop dividing but remain alive. They can collect in tissues and release inflammatory substances that may disturb nearby cells, a process linked in the study material to health problems that become more common with age.

The researchers reported that removing or blocking PD-L2 in mice reduced the accumulation of senescent cells and lowered inflammatory substances released by those cells. The mice also showed better sugar processing and greater grip strength, according to the ScienceDaily report based on Cedars-Sinai materials.

“Our findings suggest that PD-L2 may help aging cells stay in the body when they would normally be removed by the immune system,” Selim Chaib, research assistant professor of Medicine at Cedars-Sinai and first and co-corresponding author, said in the release.

The team also examined human cells and tissues. Senescent human cells produced more PD-L2 than younger cells, and PD-L2 levels rose with age in certain human tissues, according to the release.

Those human findings are supportive but not proof that blocking PD-L2 would work as a treatment in people. The study cannot show that PD-L2 blockade was linked to longer life, disease prevention or safe improvements in strength or blood-sugar regulation in humans.

James Kirkland, director of the Center for Advanced Gerotherapeutics and senior author, said the protein could become a therapeutic target if further work supports the approach. “If we can find a way to block this protein, we may be able to help the immune system get rid of these cells and potentially improve health problems linked with aging,” he said.

The study also raises the possibility that PD-L2 could be used as a blood marker to detect and monitor senescent cells. The release did not report validation of such a test against a clinical reference standard.

Funding listed in the release included the US National Institutes of Health, the Connor Fund, the Hevolution Foundation, the Noaber Foundation, Japanese science agencies and the Glenn Foundation for Medical Research. Disclosures included patents or pending patents related to PD-L2 and senolytic drugs, licensing to Rejuveron Senescence Therapeutics, and financial interests among several authors.

Future studies will examine whether blocking PD-L2 is safe and whether it produces meaningful health benefits in humans, according to the release. No dated human trial readout was provided.

Source: peer-reviewed study in Cell Metabolism and ScienceDaily/Cedars-Sinai Medical Center release, Oct. 14, 2026.

Atlas360 reports health research and does not provide medical advice.