Your skin is crawling with zombie cells–some help, some hurt
Zombie cells are those that have outlived their usefulness, but don’t really die. CREDIT: Natthawat via Getty Images.
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Your skin is crawling with zombies. Zombie skin cells, that is. This sci-fi sounding term is used to describe senescent skin cells that have outlived their usefulness, but don’t ever really die. While some senescent cells can cause problems like inflammation and speeding up aging elsewhere in the body, others can help the immune system heal wounds.
Now, we may know why zombie skin cells have this double agent-esque existence. Not all senescent skin cells are the same. There are actually three subtypes, with distinct shapes, biomarkers, and functions. Understanding the differences could help scientists target the harmful types of cells while leaving the helpful ones. The findings are described in a study published April 25 in the journal Science Advances.
“We’ve known that senescent skin cells are different from senescent immune cells or senescent muscle cells. But within a cell type, senescent cells are often considered the same—in essence, skin cells are either senescent or not, for example,” Jude Phillip, a study co-author and biomedical engineer at Johns Hopkins University, said in a statement. “But we’re finding that when a skin cell goes into senescence, or a zombie-like state, the cell could go down one of three different paths, each leading to a slightly different subtype.”
Comparing skin cells
In the new study, the team used machine learning and imaging technology to compare skin cell samples. The samples came from 50 healthy donors between the ages of 20 and 90 who participated in the Baltimore Longitudinal Study of Aging. This NIH-funded project is the longest ongoing study of aging in the United States.
The team extracted cells called fibroblasts from the skin. Fibroblasts produce the internal scaffolding that give skin tissues their structure. They pushed the fibroblasts towards senescence by damaging their DNA, which happens with aging. Senescent cells build up naturally as people grow older, so the aged samples in the lab eventually contained a mixture of healthy/nonsenescent and senescent fibroblasts.
Next, they used specialized dyes to capture images of the cells’ shapes and stained the elements that are known to indicate senescent cells. The algorithms developed for the study then analyzed the images, measuring 87 different physical characteristics for each cell, and sorting the fibroblasts into groups.
Skin-related fibroblasts with nuclei stained green and f-actin stained red. CREDIT: Jude Phillip, Johns Hopkins University.
The three types of ‘zombie cells’
They found that fibroblasts come in 11 different shapes and sizes. Three of these are distinct to senescent skin cells and the researchers labeled them C7, C10, and C11. Only one subtype of senescent fibroblast–C10–was more prevalent in older donors.
To look closer, the team placed each subtype into petri dishes and exposed them to the existing drug regimens designed to target and kill zombie cells. Each subtype responded differently when exposed to these therapeutics. For example, Dasatinib + Quercetin, a drug currently being tested in clinical trials, most effectively killed C7 senescent fibroblasts. However, Dasatinib + Quercetinbut was more limited in killing the age-associated C10 senescent fibroblasts.
While more research is needed to verify which fibroblast subtype is harmful and which is helpful, the results here show that drugs can target one subtype and not the others. More harmful zombie cells can contribute to aging-related diseases including dementia, cardiovascular disease, and diabetes as well.
“With our new findings, we have the tools ready to develop new drugs or therapies that preferentially target the senescence subtype that drives inflammation and disease as soon as it is identified,” Phillip said.
Applications in cancer treatments
In the future, more precise targeting of senescence could benefit cancer treatments. Researchers are tailoring certain therapies to trigger senescence in cancer cells, by converting the uncontrollably replicating cancer cells into zombie cells. These types of therapies could stop tumor growth, but leave senescent cells in their wake.
Conventional chemotherapies also move cells like fibroblasts towards senescence as a side effect. For patients, this buildup of senescent cells can be problematic, as those cells may promote inflammation when the immune system is at its most vulnerable.
Patients can also benefit from drugs given after chemotherapy that works like a precise zombie cell broom and sweeps up the messy cells, while leaving the more helpful ones behind. These types of treatments are called senotherapies.
The team from this study plans to look at senescence subtypes in tissue samples beyond the lab to see how those three subtypes might be associated with skin diseases and age-associated diseases.
“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.”
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