What Are Senescent Cells?
Senescent cells are often called “zombie cells” because they stop dividing but do not die. They enter a state of irreversible cell cycle arrest, meaning they can no longer multiply, yet they remain metabolically active. Unlike healthy cells that undergo programmed cell death when damaged, senescent cells resist this process, persisting in tissues.
These cells exhibit several changes, including an enlarged and flattened shape and altered metabolism. They also show specific molecular markers, such as the absence of proliferative proteins. While their inability to divide prevents the spread of damaged genetic material, their continued presence can have broader implications for the body.
How Cells Become “Zombie-Like”
Cells enter a senescent state as a protective measure, preventing the uncontrolled multiplication of damaged cells. A primary trigger is DNA damage, which can result from various internal and external stressors. Damaged DNA activates pathways that halt the cell cycle, leading to senescence.
Another common cause is telomere shortening, which occurs naturally each time a cell divides. Telomeres are protective caps at the ends of chromosomes; once they reach a critical length, they signal the cell to stop dividing, preventing further genetic erosion. Beyond these, general cellular stress can also induce senescence.
The Impact of Zombie Cells on the Body
Once established, senescent cells negatively influence their surroundings through the Senescence-Associated Secretory Phenotype (SASP). These cells release inflammatory molecules, growth factors, and enzymes. This secreted cocktail promotes chronic inflammation and disrupts the function of neighboring healthy cells.
The accumulation of senescent cells and their SASP contributes to a persistent, low-grade inflammatory state throughout the body, sometimes called “inflammaging.” This chronic inflammation is implicated in a variety of age-related conditions, including cardiovascular diseases, neurodegenerative disorders, osteoarthritis, and metabolic diseases. The SASP can even induce healthy cells to become senescent, creating a cycle that further spreads cellular dysfunction.
Targeting Zombie Cells for Health
Research explores ways to address senescent cells, primarily through two strategies: senolytics and senomorphics. Senolytics are compounds designed to selectively eliminate senescent cells by triggering their programmed death, a process called apoptosis. These agents target specific survival pathways that senescent cells use to resist dying.
Senomorphics aim to modify the harmful secretions of senescent cells without necessarily destroying them. These compounds work by modulating the SASP, reducing the release of inflammatory and tissue-damaging molecules. Both approaches show promise in preclinical studies for delaying or alleviating various age-related conditions and are currently being investigated in human clinical trials.