- a form of programmed cell death which occurs throughout development and as a mechanism to eliminate damaged cells
- a state of permanent cell cycle arrest after sustained DNA damage
- the collection of secreted factors released by senescent cells
Throughout our lives, the cells in our bodies can experience external damage from the sun or chemicals in our environment., but damage also occurs internally as a result of natural processes like metabolism. Normally, our cells are pretty good at repairing and coping with damage that occurs. However, as we get older, our repair systems start to break down and cellular damage can have some pretty detrimental effects. There are a few different things that can happen once cell damage occurs. Ideally, the damage gets repaired, and the cell goes right back to its normal function. However, sometimes the cell is irreparably damaged, so it dies in a controlled manner to stop anything bad from happening to surrounding cells and tissues. We refer to this programmed cell death as apoptosis. Unfortunately, sometimes cellular damage can lead to cancer, which happens when the cell’s DNA is altered in a way that leads to increased proliferation. The final response to cellular damage is senescence. This term might be the most unfamiliar to you, so let's take a deeper dive into the causes and consequences of cellular senescence.
The concept of senescence was first discovered in the 1960’s by two scientists named Leonard Hayflick and Paul Moorhead. Since then, many research teams have become interested in determining the hallmarks of cell senescence, the factors that induce it, and the effect of senescence on other cells and the body as a whole. While there are ongoing research projects to define new markers or causes of senescence, we do know that senescence can be induced by damage to DNA, shortening of telomeres (which are the protective caps at the end of DNA molecules), mitochondrial damage, and something called epigenetic factors, which refers to changes to our chromosomes that affect the way DNA is packaged and genes are expressed.
As the interest in defining senescent cells has grown, so has the interest in deciphering why they exist in the first place. The leading hypothesis for why senescent cells exist is that they serve as a preventative measure against cancer. The best option would be for a cell to successfully repair any damage that occurs, but when this isn’t possible (and the damage hasn’t reached a critical level of inducing apoptosis) a cell will become senescent to try and avoid becoming cancerous. Instead of devolving into unchecked proliferation, it undergoes a permanent arrest of the cell cycle which could prevent cancers from growing rapidly. Because they are no longer dividing, it might sound like senescent cells are inactive and prevent cancer by completely shutting down. In reality, senescent cells are highly metabolically active which means that there are still many cellular processes happening within the cytoplasm. Senescent cells secrete various proteins and molecules that cause inflammation. These signals can help recruit immune cells to clear up cellular damage and these molecules can also support tissue repair and remodeling. These secreted factors are collectively referred to as the senescence-associated secretory phenotype or the SASP.
So far, it seems like cellular senescence is a great mechanism to have in our bodies, but as is the case with many cellular processes, too much of a good thing can become a bad thing. Senescent cells are great for the initial prevention of cancer, but remember the SASP I just mentioned? Well, it turns out that some of those inflammatory proteins and molecules that make up the SASP can have negative effects on other cells and tissues. Although senescent cells start out as helpers that prevent cancer, too many of them can become a detriment to human health. Researchers have found that senescent cells accumulate around the body as we age, so conditions such as Alzheimer’s disease, heart disease, and liver fibrosis may be significantly worsened by the increased inflammation that comes with the accumulation of senescent cells. There is still a lot to be discovered about how senescent cells work and scientists are very interested in understanding what other roles they might be playing in a wide variety of diseases. This has also prompted many research groups to investigate how we might be able to remove senescent cells around the body with drugs or cell therapies which could help improve the health of many individuals.