Study Identifies Three Subtypes of Senescent Skin Cells

Senescent skin cells, sometimes called zombie cells, persist in the body, contributing to inflammation and disease while paradoxically aiding wound healing. Recent research from Johns Hopkins University reveals these cells are not uniform but exist as three distinct subtypes with unique shapes, biomarkers, and functions—a discovery that could enable therapies to selectively eliminate harmful cells while preserving beneficial ones. 

Using machine learning and advanced imaging, researchers analyzed fibroblast cells from 50 healthy donors (ages 20–90). They induced senescence by damaging DNA in fibroblasts, which provide structural support to tissues, to study how aging impacts these cells. Aged samples contained a mix of healthy and senescent fibroblasts, which were stained and imaged to assess physical traits. Algorithms analyzed 87 characteristics per cell, categorizing them into groups.

Fibroblasts come in 11 different shapes and sizes, three of which are distinct to senescent skin cells, the researchers found. Only one subtype of senescent fibroblast, which the researchers named C10, was more prevalent in older donors. 

In the petri dishes, each subtype responded differently when exposed to existing drug regimens designed to target and kill zombie cells. Dasatinib + Quercetin, a drug being tested in clinical trials, for example, most effectively killed C7 senescent fibroblasts but was limited in killing the age-associated C10 senescent fibroblasts. 

“We now have tools to develop drugs targeting harmful senescence subtypes,” said Jude Phillip, senior author of the study published in Science Advances. The findings hold promise for cancer treatment, where therapies inducing senescence in tumors risk leaving behind inflammation-promoting zombie cells. Senotherapies could remove these cells post-chemotherapy, reducing side effects.

The team plans to study senescence subtypes in tissue samples to link them to skin diseases and age-related conditions. “We hope, with some more development, our technology will be used to help predict which drugs might work well for targeting senescent cells that contribute to specific diseases,” Phillip said. “Eventually, the dream is to be able to provide more information in a clinical setting to help with individual diagnoses and boost health outcomes.”