Inhibiting Immune Pathway Restores Capacity to Eliminate Non-Dividing Senescent Cells

A team led by Cedars-Sinai Health Sciences University investigators has identified a protein that may hide aging cells from the body’s immune system, allowing them to build up and contribute to age-related health problems.

The findings, published in Cell Metabolism, suggest that the protein, called PD-L2, could serve as a target for treatments designed to remove harmful aging cells or as a blood marker that helps researchers track them.

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

These harmful aging cells, called senescent cells, become damaged and stop dividing but do not die. The cells remain in tissues and release substances that promote inflammation and interfere with the function of nearby cells. Their buildup has been linked to age-related health problems.

Investigators found that in laboratory mice, removing or blocking PD-L2 reduced the number of aging cells and levels of the inflammatory substances they produce. The mice were better able to process sugar and could grip objects with greater strength.

Investigators also found that human aging cells produced more PD-L2 than younger cells, and levels of the protein increased in some human tissues with age.

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.”

James Kirkland, MD, PhD, Study Senior Author and Director, Center for Advanced Gerotherapeutics

Future research will explore whether blocking PD-L2 can safely produce health benefits in human patients and help researchers better understand its role in age-related diseases.