Sennescent skin cells, often called zombies cells because they have survived their usefulness without dying, have existed in the human body as an apparent paradox, causing inflammation and promoting diseases while helping the immune system to heal wounds.
The new findings can explain why: not all senescent skin cells are the same.
Researchers at Johns Hopkins University have identified three subtypes of senescent skin cells with different shapes, biomarkers and functions, an advance that could equip scientists with the ability to point and kill harmful types while leaving intact tools.
The findings were published today in the magazine Scientific advances.
“We have known that senescent skin cells are different from senescent immune cells or senescent muscular cells. But within a type of cells, senescent cells are often considered the same: in essence, skin cells are senescent or not, for example,” said Jude Phillip, assistant professor of biomedical engineering at the Johns Hopkins University. “But we are discovering that when a skin cell enters senescence, or in a zombie state, the cell could follow one of the three different paths, each with a slightly different subtype.”
Taking advantage of the new advances in automatic learning technology and images, the researchers compared samples of cutaneous cells of 50 healthy donors between the ages of 20 and 90 that participated in the longitudinal study of Baltimore, a project funded by NIH that is the longest study of aging in the United States.
The researchers extracted fibroblasts, cells that produce scaffolding to give the tissues their structure, associated with skin tissue and pushed them towards senescence when damage their DNA, something that happens with aging. Because senescent cells accumulate naturally as people grow old, aged samples contained a mixture of healthy/non -veinscent and senescent fibroblasts.
Using specialized dyes, researchers were able to capture images of the shapes of the cells and stained elements that are known to indicate senescent cells. The algorithms developed for this study analyzed the images, measured 87 different physical characteristics for each cell and classified the fibroblasts in groups.
The researchers found that the researchers found that fibroblasts come in 11 different shapes and sizes, three of which are different from senescent skin cells. Only a subtype of senescent fibroblasts, which the researchers called C10, was more frequent in major donors.
In Petri’s dishes, each subtype responded differently when exposed to existing drug regimes designed to attack and kill zombie cells. Dasatinib + Quercetina, a medication that is being tested in clinical trials, for example, the most actually killed C7 senescent fibroblasts, but limited to killing senescent fibroblasts C10 associated with age.
Although more research is needed to verify which subtype of fibroblasts is harmful and what is useful, the results show that drugs can point to a subtype and not others.
“With our new findings, we have the tools ready to develop new medications or therapies that preferably go to the subtype of senescence that drives inflammation and disease as soon as it identifies,” Phillip said.
The most precise orientation of senescence could benefit cancer treatments, the investigators said.
Certain therapies are being designed to trigger senescence in cancer cells, converting uncontrollably replicating cancer cells into dead zombie cells in the water. While these therapies could stop tumor growth, they leave senescent cells in their path. Conventional chemotherapies also push cells such as fibroblasts towards senescence as a side effect. The accumulation of senescent cells during treatment can be problematic since these cells can promote inflammation at a time when a patient’s immune system is more vulnerable.
Patients can benefit from a medication administered after chemotherapy that can sweep the disaster, eliminating harmful senescent cells while leaving the useful senescent cells behind. This type of drugs are called Snotherapias.
Next, the researchers plan to analyze the subtypes of senescence in tissue samples, not only in Petri bottles and dishes, to see how these subtypes could be associated with various skin diseases and age associated with age.
“We hope that, with a little more development, our technology is used to help predict which medications could work well to attack senescent cells that contribute to specific diseases,” Phillip said. “Eventually, the dream is to be able to provide more information in a clinical environment to help with individual diagnoses and increase health results.”