The phenomenon of cell division means that the cells in our bodies renew through division. Unfortunately, this does not go on indefinitely, cells can replicate a certain number of times, that’s called replicative senescence. The maximum number of divisions a cell is capable to make decreases with age. Senescent cells are dysfunctional but unlike other cells, they’re resistant to apoptosis, meaning they don’t die and accumulate in various tissues in our bodies. Senescent cells are also pathogenic and have general and local damaging properties. In the near future, we should be able to remove senescent cells. One of the reasons why is to make them sensitive to apoptosis again.
Want to learn more? Keep reading the article by Prof. Jacques Proust.
The cells in our body renew themselves by cell division, with each mother cell giving rise to two daughter cells. This division is preceded by the doubling of the cell content: any damaged cell components are diluted by newly synthesised ones, which constitutes an effective regeneration mechanism.
However, this phenomenon of cell division does not reproduce itself indefinitely and human cells in culture can only replicate a certain number of times, which is called “replicative senescence”.
Interestingly, the maximum number of divisions a cell is capable of performing decreases with the age of the donor. However, there is considerable inter-individual variability and the theory that the number of cell divisions in vitro may reflect the donor’s physiological age and/or life expectancy is obviously wrong.
When a young cell is damaged or its function is impaired, it activates a suicide programme called apoptosis and quietly disappears from the body without triggering an inflammatory response. The situation is quite different for senescent cells. Although they are dysfunctional, they are resistant to apoptosis, do not die and gradually accumulate in the various tissues of our body.
A large number of these senescent cells will acquire what is known as a “secretory phenotype” which is characterised by the production of various molecules (inflammation mediators, collagen-destroying enzymes, oxidising free radicals, etc.) directly involved in the ageing process itself and/or in the exacerbation of age-related pathologies. In addition, these cells will contaminate adjacent cells and induce the senescent phenotype in them.
Senescent cells are pathogenic and have general as well as local damaging capacities. Experimentally, the transplantation of a small number of these senescent cells into the tissues surrounding a joint rapidly induces inflammatory manifestations in this joint similar to those observed in non-infectious osteoarthritis.
More globally, the activation by senescent “secreting” cells of transcript factors and genes involved in the mechanism of inflammation contributes to the chronic inflammation observed during ageing, a phenomenon known as “inflammaging”. The production of oxygen free radicals oxidises the various components of neighbouring cells and seriously disrupts their function. The release of proteolytic enzymes (metalloproteases) contributes to tissue breakdown and skin ageing.
Recent studies show that the secretory phenotype of senescent cells plays an important role in the appearance of multiple diseases associated with ageing such as cancer, diabetes, atherosclerosis, cardiovascular diseases, emphysema, chronic obstructive pulmonary disease, pulmonary fibrosis, osteoarthritis, osteoporosis, degeneration of the intervertebral discs, neurodegenerative diseases, macular degeneration, etc.
In the near future, the elimination of senescent cells will take pride of place among the various biomedical interventions designed to slow down ageing or limit its consequences. One of the therapeutic strategies chosen to eliminate these cells is to make them sensitive to apoptosis again. The immune system can also be activated so that its effector cells specifically destroy senescent cells. New classes of so-called ‘senolytic’ drugs will soon be part of the anti-ageing pharmacopoeia.
