Researchers at Cedars-Sinai say they have identified a protein that helps aging, damaged cells hide from the immune system — a mechanism that may explain why so-called senescent cells accumulate in the body over time and drive chronic inflammation linked to aging. The findings, published Thursday in Cell Metabolism, point to the protein PD-L2 as both a possible drug target and a blood marker for tracking these cells.
Senescent cells stop dividing but do not die, instead lingering in tissue and secreting inflammatory molecules that interfere with neighboring cells — a process researchers call the senescence-associated secretory phenotype. Normally, the immune system is supposed to clear out these damaged cells, but the Cedars-Sinai team found that senescent cells that produce high levels of PD-L2, an immune checkpoint protein, appear able to evade that surveillance and persist.
"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, a research assistant professor of medicine at Cedars-Sinai and the study's first and co-corresponding author, in a statement carried by Medical Xpress.
Mouse data, human hints
In laboratory mice, removing or chemically blocking PD-L2 reduced both the number of senescent cells and the levels of inflammatory substances they released. Treated mice also processed blood sugar more efficiently and had stronger grip strength than untreated animals — two measures researchers commonly use as proxies for metabolic and physical aging in rodents.
The team also examined human tissue and found that senescent cells produced substantially more PD-L2 than healthy, dividing cells, and that PD-L2 levels rose in some tissues as people aged. According to the Cedars-Sinai announcement, circulating PD-L2 in blood also declined in people who underwent senolytic treatment — drug regimens designed to clear senescent cells — hinting that the protein could double as a marker for monitoring how well such therapies work.
The results remain preclinical: the functional experiments blocking or removing PD-L2 were conducted only in mice, and the human data so far are observational, drawn from tissue samples and blood measurements rather than a clinical trial. Cedars-Sinai researchers say the next step is to test whether blocking PD-L2 can safely reduce senescent-cell burden in people, and whether doing so translates into measurable health benefits rather than simply reshuffling immune activity elsewhere in the body.
If confirmed in further studies, the discovery would add PD-L2 to a small list of molecular targets — alongside other immune checkpoint and senolytic pathways already in early human trials — that researchers are pursuing in the broader push to treat aging itself as a modifiable biological process rather than an inevitable decline.
