Replicative senescence

Definition

Replicative senescence is a phenomenon seen in most animal cells where each cycle of cell division (called a passage) makes the cell more "senescent" (closer to death). For a given cell, there's generally a limit on the maximum number of passages that it can go through. The value of the limit for human somatic cells is termed the Hayflick limit; the Hayflick limit is about 40 to 60.

Replicative senescence is not seen for some kinds of animal cells, such as stem cells and cancer cells.

Causes

There are different theories as to the causes of replicative senescence. The causal theories would also need to explain the cells that escape replicative senescence.

Telomere shortening

Telomere shortening is one mechanism of replicative senescence; it is not clear if this is the dominant mechanism.

The DNA associated with the cell has repetitive sequences at the end called telomeres. During cell division, the ends of the DNA get stripped off; since these ends are telomeres, the telomeres get shortened each time. If there were no process for restoring the telomeres, the telomere keeps shortening and eventually runs out.

There exists a ribonucleoprotein called telomerase that lengthens the telomere to compensate for the telomere shortening. However, this ribonucleoprotein isn't active in all cases and even when it is, it may not be active enough to fully compensate for telomere shortening. For instance, in normal human somatic cells, the activity of telomerase is almost zero, so it fails to compensate for the telomere shortening at each cell passage.