Cellular senescence refers to the state in which normal cells lose the ability to divide. This is typically a result of the cell’s response to stress or damage, particularly to its DNA. Senescence acts as a critical barrier against the development of cancer, preventing the proliferation of damaged cells that might otherwise form a tumor.
There are several mechanisms, or “barriers,” that induce cellular senescence:
- Replicative Senescence: This is triggered by the gradual shortening of telomeres, which are the protective caps on the ends of chromosomes. Each time a cell divides, its telomeres shorten, and when they become too short, the cell can no longer divide and enters a state of senescence. This mechanism limits the number of times a cell can divide and is also known as the Hayflick limit.
- Oncogene-Induced Senescence (OIS): This type of senescence is induced when oncogenes, which are genes with the potential to cause cancer, are overly active. This overactivity can cause DNA damage and metabolic stress, leading the cell to halt division and enter senescence as a protective mechanism to prevent the formation of a tumor.
- Stress-Induced Premature Senescence (SIPS): This can occur in response to various forms of cellular stress, such as oxidative stress, DNA damage (not related to oncogene activation), or the activation of certain tumor suppressor genes like p53.
These barriers are crucial for preventing the proliferation of damaged cells and suppressing tumor development. However, senescent cells can also contribute to aging and age-related diseases, as they accumulate over time and can promote inflammation and tissue dysfunction. Understanding the mechanisms of senescence and how to manipulate them is a major focus of research in cancer biology and aging.
