Scientists discover how harmful “zombie cells” hide from the immune system
Scientists have discovered a protein that may help harmful aging cells hide from the immune system, allowing them to accumulate and fuel age-related health problems. Blocking the protein in mice reduced these cells and inflammation while improving blood sugar regulation and strength, offering a promising new direction for anti-aging research.
Key points
- Cedars-Sinai researchers identified PD-L2 as a protein that helps aging cells evade immune clearance.
- Blocking PD-L2 in mice reduced senescent cells and improved sugar processing and grip strength.
- Human senescent cells produced more PD-L2, and levels rose with age in certain tissues.
Researchers led by Cedars-Sinai Health Sciences University have identified a protein, PD-L2, that may allow harmful aging cells to escape detection by the immune system. The discovery, published in Cell Metabolism, points to PD-L2 as a possible target for therapies aimed at eliminating these cells and as a blood marker for detecting and monitoring them.
As cells age or become damaged, some enter a state called senescence, in which they stop dividing but remain alive in tissues. Their accumulation has been linked to inflammation and health problems that become more common with age.
Experiments in mice
In laboratory mice, removing or blocking PD-L2 reduced the buildup of senescent cells and lowered levels of the inflammatory substances they release. The mice also showed improvements in their ability to process sugar and greater grip strength, suggesting the protein may influence physical functions affected by aging.
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
Human cells and next steps
The team found that senescent human cells produced more PD-L2 than younger cells, and that levels of the protein rose with age in certain human tissues. The results suggest the mechanism seen in mice may also be relevant to human aging, though more research is needed before the approach can be considered for treating people.
Selim Chaib of Cedars-Sinai said, "PD-L2 may help aging cells stay in the body when they would normally be removed by the immune system." James Kirkland, the study's senior author, said blocking the protein might help the immune system eliminate these cells and potentially improve health problems linked with aging.
