SENESCENCE

Cellular senescence: what is it and why is it important?

With “cellular senescence” we refer to a situation in which cells become “old”, stop replicating and begin to produce specific molecules that recall the immune system to eliminate them and replace them with new “fresh” cells, able to replicate and do their job.

Cell senescence is therefore a physiological process, functional to cell renewal. Various studies also illustrate how this mechanism corresponds to a specific form of protection of the organism from pathologies, primarily oncological ones, since, by slowing down the replication of cells, the possibility of growth of possibly mutated cells is blocked in the bud. The recall of the immune system also allows the elimination of any cells with malignant characteristics that can therefore be replaced by new and normal ones.

However, cellular senescence is not always a positive process. With advancing age, in fact, the efficiency of the immune processes in eliminating senescent cells is reduced. Aged cells accumulate in body tissues, which can promote diseases related to advancing age, such as cancer or chronic inflammatory states.

Furthermore, cellular senescence is not a process that ends with the elimination of the “aged” cell alone. We have seen how these cells release certain substances, called SASP (Senescent Associated Secreted Phenotype), capable not only of initiating the inflammatory process, but also to modify the behavior of neighboring cells. SASPs, for example, are seen as growth factors by cancer cells and for this reason they are to be considered risk factors.

The shadows of senescence

Non-physiological senescence

However, cellular senescence is not always a physiological process. It was in fact discovered, as illustrated by a recent study published in the journal Nature, that some viruses can trigger the premature senescence of the affected cells as a consequence of the stress experienced.

This has been observed above all in the tissues most affected by the virus (especially nasopharynx and lung) where the high presence of SASP proteins seems to be the cause of the strong activation of the inflammatory cascade found in patients by certain viruses, thus also allowing the typical lymphocyte infiltration.

For this reason, viral infection in general is related to the induction of cellular senescence and therefore to the inflammatory processes that follow.

In recent years several molecules, both chemical or natural ones, have researched for their ability to delay the process of cellular senescence or even eliminating senescent cells, especially those originated by a viral infection. These substances are called “senolytics”. The elimination of these cells could thus be linked to a better course of the infection in which the inflammatory process is alleviated.

The most studied molecules are:

Navitoclax: synthetic molecule, still under study, reported in the literature as a senolytic agent which therefore induces the death of senescent cells but not of non-senescent ones.
Fisetin: flavonol present in many plants and fruits, especially strawberries. In laboratory trials, it appears to have demonstrated antiproliferative and senolytic activity.
Quercetin: natural molecule present in various foods such as capers, apples, grapes and onions. It is endowed with antioxidant activity and studied for its possible antiviral, antiproliferative and senolytic abilities.

How to "rejuvenate" cells?

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