Health Relevance

What is the NIH Common Fund's Cellular Senescence Network (SenNet) Program?

Cells in the human body divide from one cell into two, allowing the body to create new cells. This can be an important ability, such as when our skin replaces shed cells or a child grows taller. However, researchers have observed that a small number of these once dividing cells suddenly cease to divide, becoming senescent. Although senescent cells do not divide, they remain active. In fact, they may release a large number of molecules, many of which can have effects on nearby cells. Senescent cells play both positive and negative roles in human biology. For example, cellular senescence can be a defense mechanism, like when it stops cancerous cells from multiplying. It also can be helpful by aiding proper wound repair and development of human embryos. However, researchers have shown that senescent cells may contribute to many chronic diseases in older adults, including cardiovascular disease, Alzheimer’s disease, arthritis, lung disease, and kidney disease.

To treat the negative effects of senescent cells, researchers have recently developed a class of drugs called “senolytics” that preferentially kill senescent cells. In animal models, senolytic treatments have resulted in overall improvements in health as well as resistance to a variety of diseases. Clinical trials in humans are currently underway. Nevertheless, there are issues that must be resolved before widespread use of senolytics is possible. Senescent cells show a range of characteristics based on what triggered senescence, the tissue origin of the cell, and where the cell is located in the body. For these reasons it is difficult to identify all senescent cells based on the same criteria. Likewise, a single senolytic cannot target all senescent cells, so specialized approaches will need to be developed. Some senescent cells also play positive roles in human health and removing them with senolytics may be harmful. To understand the origin and function of senescent cells, the NIH Common Fund created the SenNet program, which aims to map senescent cells in multiple normal tissues of human and mice in three dimensions. From this, researchers will know the range of senescent cell characteristics, functions, and where these cells typically occur in the body. Researchers can also use these maps as a reference, to understand how a disease, condition, or therapy affects cellular senescence.