Death Resistant Cells
Human body cells do not lead existential lives…
…Each cell in the human body has a predetermined fate. One cell might be destined to become skin while another cell is fated to be part of the liver.
But cells can sometimes be damaged in a way that causes them to diverge from the fate into which they were born. Cancer, for example, is a process in which mutations in the nuclear DNA and other changes cause cells to adopt a more primitive lifestyle and begin the uncontrolled growth that results in the formation of a tumor.
To guard against such risks, human cells do have built-in programming that kicks on when a cell is on a course that would cause harm to the body. One programmed response to such trajectories causes the cell to commit suicide, a process known as apoptosis. Apoptosis can also be brought to bear on otherwise-healthy cells that the organism no longer needs. The animal kingdom provides an excellent example of this: the cells of a tadpole’s tail die through apoptosis when it transforms into a frog, and the tail simply disappears.
Another kind of programming provides an alternative to apoptosis in dealing with damaged or unwanted cells. This kind of programming keeps the cell alive, but it does not allow it to continue on the risky trajectory that set off the programming in the first place. This type of programming is an effective short-term protective response to an immediate danger because of the way it can “turn off” uncontrolled cell growth. At the same time, it causes the cell to adopt a different, abnormal metabolic state.
Such “senescent” are relatively harmless when they few in number, but these cells can accumulate over time, eventually reaching levels that are harmful to human tissue.
Senescent cells start out as skin cells or as cells that act in a supportive role to organs. Programming eliminates the senescent cell’s ability to divide and reproduce. This programming prevents skin cells from continuing down a path that leads to the development of cancer, for example, or halt uncontrolled growth of scar tissue cells and fibrous connective tissue after an injury.
Senescent cells secrete large amounts of proteins that cause inflammation in the immune system and degradation in supportive tissue. The negative effects of these proteins are negligible in younger people because they have only a few senescent cells in their tissues, but these as senescent cells accumulate over the decades the secreted proteins wreak havoc on nearby healthy tissue in older individuals. Tissues that contain large numbers of senescent cells are at greater risk for developing cancer, becoming inflamed and negatively affecting the immune system.
There are two main approaches to the problems associated with senescent cells: develop a drug that is toxic to abnormal cells but harmless to healthy ones, or stimulate an immune response that targets and selectively kills unhealthy cells.
Molecules lining the surface of cells help those cells interact with their surroundings; these molecules are to varying degrees distinctive to their fate. Because each type of cell has different surface molecules, these molecules can serve as markers, or identification for that cell. Liver cells have a different group of molecules on their surface than blood cells, for example.
Abnormal cells have abnormal surface molecules, making these cells easy to target for therapy. Oncologists already use this type of approach when treating some types of cancer with the intent of shutting down the cancer cells’ growth with drugs or by stimulating the immune system to do the job. In some cases, killing abnormal cells deters, treats, or prevents illnesses by making room for new, healthy cells.
Using SENS Research Foundation funding, scientists from University of Arizona are investigating ways to restore a healthy immune system in aging mice by purging unhealthy immune cells known as “anergic T-cells” to free up space for new and healthy killer T-cells. The researchers also hope to bolster the immune system by increasing the body’s ability to produce new killer T-cells.
With funding from SENS Research Foundation and working in Dr. Judith Campisi’s laboratory at the Buck Institute for Research on Aging, PhD candidate Kevin Perrott is investigating how molecules affect one type of senescent skin cell to understand its role in inflammation and the immune system. These scientists also hope to discover how to kill these senescent cells before they can cause a problem. Additionally, these researchers are testing a library of compounds to identify any that are capable of selectively targeting senescent cells.
SENS Research Foundation funding also supports research performed by Nick Schaum in the Campisi lab, which has shed light on the link between the two hallmarks of cell senescence, identifying a key driver of inflammation and halted cell division.
The goal of these research projects is to understand how cell programming can cause illness and to develop ways to control cell senescence, either through therapeutic drugs or by stimulating the immune system so that it destroys only abnormal cells while leaving healthy cells intact. Success will lead to new rejuvenation biotechnologies to prevent, treat, and even reverse the course of the disease and disability caused by these abnormal cells.