Scientists are reaccessing the role of “zombie” cells in the body that were once seen as nothing more than a hindrance to healthy aging. These senescent cells, which no longer divide or support the tissue around them, were long thought to be a major cause of age-related inflammation and degeneration. But new research is beginning to show that these cells may perform some important functions in the body and that eliminating them may not be the best way to achieve long and healthy life.
A recent study conducted by UC San Francisco reported that not all Senescent cells are harmful and need to be eliminated. Some of them are located in young, healthy tissues and help with the repair process. Scientists have discovered that these cells are not only active in lung tissue but also in other organs in the body that serve as barriers, such as the colon, small intestine, and skin. When senolytic drugs were used to kill these cells, it led to slower healing times for injuries to lung tissues.
According to Tien Peng, MD, associate professor of pulmonary, critical care, allergy, and sleep medicine, and senior author of the study, senescent cells can help with the repair process by acting as ‘sentinels’ that detect tissue damage and stimulate nearby stem cells to begin growing and repairing the area.
Cells Responsible For Aging Can Cause Both Damages And Heal
Peng continued by stating that, at first, it makes sense that scientists would view senescent cells as purely harmful. As people age, their bodies accumulate more and more senescent cells – these are old cells that no longer have the ability to make new ones. Unlike normal cells that die when they age, senescent cells don’t. They keep living and releasing a mixture of inflammatory substances called the SASP. Hence these cells are names zombie cells. These aging-related conditions include Alzheimer’s disease, arthritis, cancer, and more.
Researchers discovered that by using senolytics to target and kill “zombie cells,” they could prevent or diminish age-related diseases and extend the lifespan of animals. After this finding, many research labs and pharmaceutical companies have been focused on discovering more powerful versions of these drugs. However, Peng warns that killing senescent cells has dangers; on the basis of the current study, these same cells have the ability to spur normal healing by activating stem cell repair. In addition, Peng said that their most recent study found senolytics could negatively impact healthy cell repair. However, they also noted that senolytic therapies have the potential to target diseases where faulty stem cells cause cellular problems.
Activating Senescent Cells
A significant challenge to studying senescent cells is that there are few biomarkers of senescence (such as the gene p16), making it tricky to identify the cells.
To begin their research, scientists took cells known as fibroblasts and extracted them into culture dishes where they could grow and reproduce. Next, the team stressed the cells with chemicals that caused them to age. However, in a live organism, cells constantly interact with the tissues around them, which greatly impacts gene activity. This implies that cells growing unassisted in a dish often have wildly different characteristics than cells in their natural habitat.
In order to make their research more powerful, Nabora Reyes de Barboza, Ph.D. and her colleagues advanced a common technique of joining a significant gene—the p16 gene that’s excessively active in senescent cells—with a green fluorescent protein (GFP), so the location of the cells can be seen under ultraviolet light. By increasing the amount of green fluorescent protein in these senescent cells, Reyes was able to amplify the fluorescent signal. This gave researchers the ability to see senescent cells in living tissues.
Senescent Cells Help To Stimulate Stem Cells Just After Birth.
The researchers discovered that senescent cells exist more in young and healthy tissues than they previously thought. They also found that these cells begin appearing shortly after birth. Furthermore, they discovered that particular growth factors stimulate stem cells to expand and heal tissues. The fact that cells of the immune system, like monocytes and macrophages, can activate senescent cells is relevant to aging and tissue injury. This means that inflammation plays a big role in how these things affect cell activation and regeneration.
While studying the lung tissue, Peng’s team found evidence of senescent cells next to stem cells. These glowing green cells are usually located at the basement membrane. The purpose of this membrane is twofold: it keeps harmful chemicals and outside entities from entering our bodies and allows oxygen to diffuse throughout underlying tissues. Damage can occur at this dynamic interface.
The researchers saw senescent cells occupying similar positions in other barrier organs, including the colon, small intestine, and skin. When they killed these senescent cells with Senolytics, the lung stem cells were not able to properly repair the surface of the organ’s barrier. Dr. Leanne Jones, director of the UCSF Bakar Aging Research Institute, and Stuart Lindsay, Endowed Professor in Experimental Pathology said that Peng’s study is extremely important for aging research where researchers aim to help people live healthier and longer lives.
Senolytics studies should focus on targeting harmful senescent cells while leaving helpful ones alone. And these findings should emphasize more on creating drugs that target specific senescent cells implicated in disease instead of those associated with regeneration. By doing so, we can develop more effective treatments.
