Cellular Senescence and Aging: Here’s What You Need to Know

Hate it or embrace it, we all eventually face certain telltale signs of aging – the wrinkles, the gradually stiffening joints, the graying hair. But have you ever stopped to think about the process behind all of these signs? And perhaps what we can do to slow it down? Longevity and aging scientists have, and they’ve discovered some very good news. One of the primary processes behind aging, known as cellular senescence, is malleable and has the ability to be slowed down or even reversed, paving the way for potential applications aimed at extending a healthy lifespan. Keep reading to learn more about what cellular senescence is, how it’s related to aging, and how it can be reversed.



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July 15, 2020

01What is cellular senescence?

Cellular senescence is one of the nine major hallmarks of aging. Derived from the Latin root senex, meaning “old age,” a cell becomes senescent when it no longer has the ability to divide.[1]

Cellular senescence is a natural process that occurs continuously throughout our body and across our lifespan. Our cells maintain a consistent rate of turnover, dividing and replicating in order to replace the old and damaged ones. However, each cell in the human body is limited in the number of times that it can replicate due to the natural accumulation of damage with each replication. Once a cell reaches its replication limit, it enters a phase called ‘replicative senescence’, which marks the transition of a normal cell to a senescent cell.[2]

02What is the purpose of cellular senescence?

The cessation of cell replication and transition into senescence was biologically designed in our favor, as it was intended to prevent the proliferation of cells that have accumulated damage over time. It’s a milestone that can be triggered in response to internal triggers or environmental stressors that might alter DNA, such as DNA damage or oncogenic (cancer-inducing) stress.[3]


03Is senescence good or bad?

OneFact The cells of a Galapagos turtle divide approximately 110 times before senescing, whereas mice cells become senescent within 15 divisions! Once a cell stops replicating and becomes senescent, it can either undergo programmed cell death, a process termed apoptosis, or the senescent cell can linger in the tissue - this is where senescence stops working in our favor.[4] Senescent cells emit harmful factors that induce chronic inflammation, accelerate aging, and promote the onset of diseases. For example, a common characteristic of senescent cells is an increased level of reactive oxygen species (ROS), a free radical that is thought to play a critical role in skin aging and disease development.[5] Additionally, senescence-induced inflammation can trigger suppression of the immune system, which can drive tissue degeneration associated with aging and the onset of certain diseases, including cancer and other age-related disorders.[6]

04Impacts of Senescent Cells on Healthy Cells

Mapping senescent cell accumulation with age using beta-galactosidase staining. Senescent cells are shown here in blue.

And unfortunately, the damage does not end with a single cell. Like a rotten apple in a basket contaminating its neighboring apples, senescent cells behave in a similarly aggravating way to adjacent cells. Senescent cells exude pro-inflammatory factors and other chemical signals that induce senescence in healthy neighboring cells.[7] This creates an environment well-suited for the development of chronic diseases. To make matters worse, senescent cells are also able to secrete factors that actually recruit immune cells to enter into senescence, thereby reducing the number of immune cells available to fight pathogens and other damaging stimuli.[8]

As a result, research demonstrates that senescent cells are regarded as one of the main drivers of aging and age-related diseases, such as cancer, Alzheimer’s, Parkinson’s disease, diabetes, osteoporosis, osteoarthritis, and cardiovascular diseases.[9],[10],[11]

05So, how does cellular senescence relate to aging?

When we are young, our bodies are able to efficiently remove senescent cells in order to make room for young and healthy cells. However, as we age, not only do we experience an increase in the production of senescent cells, but our bodies lose the ability to clear the increased number of senescent cells that we’re producing. This results in a net accumulation of senescent cells in our tissues, notably in our skin (Figure 1).


06How is senescence linked to skin aging?

An increased level of senescent cells in our skin contributes to both aesthetic aging and age-related conditions, such as an increased presence of wrinkles, a weakened skin barrier, and susceptibility to skin cancer. Once the skin barrier is compromised through an increase in cellular senescence, a cycle called inflammaging is initiated, in which the inflammation initiated by senescence triggers system-wide inflammation. When left to linger in tissues, this inflammation can lead to an increased rate of aging throughout the body and can contribute to the aforementioned age-related diseases (Figure 2).[12] Read more on skin’s impact on health here.

07Is it possible to slow down cellular senescence?

Here’s the good news. Scientists have discovered that eliminating senescent cells and preventing the accumulation of senescent cells is not only possible, but it’s an effective way of slowing aging and age-related diseases. Specifically, many studies are exploring senotherapeutic molecules that can either modulate senescence or eliminate senescent cells as ways of extending lifespan and healthspan. In fact, research has shown that by eliminating senescent cells in model organisms, such as rodents, systemic levels of inflammation can be reduced and immune function can be extended, thereby slowing and delaying the onset of age-related diseases and effectively extending the lifespan and healthspan of the organisms. In fact, senotherapeutic compounds are now being studied for their application across osteoarthritis, kidney disease, cardiovascular disease, and many other age-related disorders.[13]

08Conclusion

  • Cellular senescence is one of the nine hallmarks of aging, and occurs when a cell reaches its peak number of replications and divisions.
  • Though senescence is a biologically protective measure against the proliferation of unhealthy cells, it can actually cause widespread damage by spreading to neighboring cells.
  • Senescent cells are linked to several age-related diseases, and can cause systemic damage.
  • Fortunately, senotherapeutic compounds, which target senescent cells, are making their way to the forefront of longevity research.
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