Replicative senescence is a state of permanent cell cycle arrest that occurs after a certain number of divisions. This phenomenon was first described by Leonard Hayflick in the 1960s and is often referred to as the “Hayflick limit.” It is one of the key mechanisms that prevent the unlimited cell division that is characteristic of cancer.

Here’s how it works:

In normal somatic cells, the ends of chromosomes (telomeres) shorten each time a cell divides. Telomeres are like the plastic tips on shoelaces; they protect the ends of chromosomes and prevent them from fusing with each other. When telomeres become critically short, they can no longer protect the chromosomes, and the cell perceives this as DNA damage. In response, the cell activates a DNA damage response pathway that ultimately leads to cell cycle arrest, or senescence.

The p53 protein and the Rb protein are key players in this process. They help to halt the cell cycle and prevent the cell from dividing. Cells in a state of senescence are still metabolically active but have altered function, including changes in gene expression and often an increase in the secretion of certain inflammatory molecules, a state known as the senescence-associated secretory phenotype (SASP).

While replicative senescence is a crucial mechanism to prevent the development of cancer, it also contributes to aging and age-related diseases. As organisms age, the number of senescent cells in their tissues increases. The accumulation of these cells and the inflammatory molecules they secrete can contribute to tissue dysfunction and the development of age-related diseases.

Consequently, there is great interest in developing ways to safely remove senescent cells or modulate their function to improve health in old age, an approach known as senotherapy. However, this research is still in its early stages, and more work is needed to fully understand the role of senescence in aging and disease and how best to target it therapeutically.