What is Cellular Senescence its Causes, and Effect?

Cellular Senescence Definition

Cellular senescence is a state in which cells can no longer divide. This permanent state entails benefits and detriments for the organism in which the cells live. Whereas cellular senescence was first attributed to tumor suppression and aging, more recent research has found that it also promotes cancer and tissue repair. Therefore, the effects of cellular senescence in the organism vary according to a number of factors, such as age.

Senescent cells have a series of features that characterize them. Besides not being able to divide anymore, senescent cells are larger than normal cells, and they express and secrete certain molecules that normal cells do not secrete, or do so in smaller quantities (e.g., senescence-associated beta-galactosidase or SA-Bgal, the tumor suppressor p16INK4a, growth factors, and cytokines, among others).

Causes of Cellular Senescence

What causes a cell to stop dividing? There are several causes, some of which are telomere erosion, other types of DNA damage, and other factors that act independently of DNA damage.

Telomere Erosion

The most widely known cause of ceased cell division is telomere erosion. Telomeres are sequences of DNA that are found at each end of the chromosomes. They consist of a DNA sequence of repeated nucleotides; for instance, the repeated nucleotides in human telomeres are TTAGGG, and these extend to 11 kilobases at birth. These repetitions protect the chromosomes from losing important information during replication and from fusing with nearby chromosomes.

In each replication, the telomeres lose a small part of DNA because the enzymes responsible for duplicating the DNA cannot reach the end of the chromosome. Thus, the chromosomes are shortened after each replication until they reach a point at which, after having lost the telomere, they lose important genetic information. At this point, cells undergo a DNA damage response (DDR); they can no longer divide and they are thus considered senescent. Because this is a natural process of aging, more cells become senescent as we grow older. In fact, old people have telomeres of fewer than 4 kilobases of length—almost a third of the length they are at birth.

Other Types of DNA Damage

In addition to telomere erosion, other types of DNA damage can also induce cellular senescence by damaging DNA. The most common cause is DNA double strand breaks, which bring about the DDR and consequently make cells senescent. Other examples that also act through the DDR include the presence of mitogenic signals, reactive oxygen species or certain proteins that promote cell growth and proliferation.

Other Factors

Finally, among other senescence inducers that act independently of DNA damage are changes in DNA-associated proteins (e.g., chromatin), abnormal expression of some proteins (e.g., tumor suppressors) and the presence of signaling molecules that alter cellular functions (e.g., cellular stress).

Effects of Cellular Senescence

Cellular senescence was first thought to have evolved to prevent tumor growth. Because this phenomenon does not allow cells to divide anymore, cellular senescence could be a mechanism to avoid the division and spread of cancer cells. This tumor suppression effect had already been observed when cellular senescence was first described in the 1960s.

Though counterintuitive, another effect of cellular senescence is tumor growth. This deleterious consequence can be attributed to age: whereas cellular senescence in young organisms protects against tumors, in older organisms it induces the spread of tumors. The hypothesis behind this is that age-related disorders and phenotypes, among which is cancer-inducing cellular senescence, did not evolve with natural selection (i.e., did not evolve to enable the fittest to survive) because the chances of arriving at old age are rarer than the chances of acquiring disorders or phenotypes during youth for which natural selection has established mechanisms of defense. In other words, the chances of getting a tumor at a young age, for which natural selection has established defense mechanisms such as cellular senescence, are higher than the chances of surviving to older ages, when tumor growth is more likely to occur.

Finally, another hypothesized effect of cellular senescence is tissue repair. Senescent cells, as mentioned above, secrete a variety of molecules, among which are growth factors and other proteins involved in wound healing and signaling of pathogens that immune cells detect and get rid of. Therefore, studies support that senescent cells play a role in repairing tissue directly and also in secreting signaling molecules for other mechanisms in the organism to detect and repair tissue.

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