Cellular senescence contributes to degenerative aging. The burden of senescent cells increases throughout the body with age, and these cells disrupt tissue function and health via their inflammatory secretions. Senescence is an end state in nature, irreversible once a cell has become senescent. Researchers have nonetheless found ways to force cells out of senescence, and while this line of work is not very advanced, it has been suggested as the basis for alternatives to senolytic therapies that force the destruction of senescent cells.
The majority of cells entering senescence do so because their telomeres have shortened due to cell division, reaching the Hayflick limit, not because they became damaged and potentially cancerous. But reversing senescence has always come with the accompanying question of what to do about cells that are senescent due to mutational damage to the genome: returning potentially cancerous cells to normal operation does not seem like a good idea. Researchers here expand the importance of that question. It seems plausible that all senescent cells have significant levels of genomic damage, generated on entry to senescence, regardless of the cause of senescence.
Researchers have shown that cellular senescence, which occurs when aging cells stop dividing, is caused by irreversible damage to the genome rather than simply by telomere erosion. This discovery goes against the scientific model most widely adopted in the last 15 years, which is based on one principle: telomeres, caps located at the ends of chromosomes whose purpose is to protect genetic information, erode with each cell division. When they get too short, they tell the cell to stop dividing, thus preventing damage to its DNA. Made dormant, the cell enters senescence.
"What's most surprising is that, before really entering senescence, the cells divide one last time. In fact, the cell division caused by telomere dysfunction is so unstable that it ends up creating genetic defects. Contrary to what was believed, senescent cells have an abnormal genome. That's what we show in our study. Genetically, we were able to reproduce the phenomenon of cellular aging in the laboratory and ensured that all the telomeres of a population of cells became dysfunctional. With our equipment, we then observed in real time what was happening inside each single cell."
With time, senescent cells build up in the body and are responsible for the development of diseases such as cancer. This study, therefore, opens up new research opportunities. For example, could telomeres be repaired prior to the senescence phase, thereby preventing cellular aging and genomic instability? The scientific community has been debating this potential cellular rejuvenation for several years now. Nevertheless, these emerging therapeutic approaches still need fine-tuning.