What Is Senescence & Its Relationship To Aging?

What Is Senescence & Its Relationship To Aging?








Reference Lab

JAN 12, 2023
UPD: MAY 3, 2023


Hate it or embrace it, we all eventually face certain telltale signs of aging – wrinkles, gradually stiffening joints, graying hair. But have you ever stopped to wonder what causes these signs in the first place?

The answer is cellular senescence: one of the primary processes behind biological aging. Across decades of research, longevity scientists have discovered that this cellular phenomenon impacts all measures of human health– from skin damage to age-related diseases like Alzheimer’s or cancer. But it’s not all bad news: unlike many biological processes, cellular senescence can be slowed and even reversed. Keep reading to learn more about cellular senescence, how it’s related to biological aging, and why it could be the key to extending our healthspan.

01What is senescence?

Cellular senescence is one of the nine hallmarks of aging and a central pillar in the development and output of each hallmark. Derived from the Latin root senex, meaning “old age,” senescence is the end stage in a cell’s life cycle when it stops dividing.

Cellular senescence is happening constantly in our bodies. When we’re young and healthy, senescent skin cells are quickly cleared away and replaced with regenerated new cells. But as we get older, more and more senescent cells accumulate. When these cells linger, they secrete biochemical signals that induce chronic inflammation, suppress the immune system, and accelerate aging in neighboring cells. These signals can even inhibit stem cell function, decreasing your tissues’ ability to regenerate.

Sound like the perfect storm? It is. Like rotten apples that spoil the bunch, senescent cells drive neighboring cells into senescence, triggering widespread damage that can make all our tissues–even our skin–act older than they actually are.1

02What is the purpose of cellular senescence?

Biologically, organismal senescence was designed to prevent unhealthy, damaged cells from replicating – stopping the proliferation of cells that are no longer functioning at their best. Cells that have been impacted by internal triggers or environmental stressors can cause issues in the body if they replicate. By turning these cells off, the body prevents damage from spreading.2

03What are the different types of cell senescence?

There are three main types of senescence, each with their own unique causes:3

 

  • Replicative - This occurs when a cell has hit its maximum number of cell divisions and should no longer replicate to prevent the potential for damaged cell proliferation. This is the classic senescing process.
  • Oncogene Induced - Oncogenes are genes responsible for cell replication. When these genes are overexpressed, they can trigger higher than normal levels of cell proliferation that can result in a tumor. To prevent this from happening, the cell activates two tumor-suppressing pathways in response to oncogene overexpression: these pathways stimulate cellular senescence, turning off the overactive cell before it becomes cancerous.
  • Stress Induced - Our bodies are constantly encountering stressors like oxidizing agents and free radicals. Some of these stressors naturally occur in the body and others exist all around us in the air we breathe and the food we eat. Some of these stressors can cause single stranded breaks (SSBs) in the DNA inside our cells. In response, our cells activate a DNA damage alert to prematurely send the damaged cell into senescence.4

04Is senescence good or bad?

Senescence is, at its core, a beneficial natural process that prevents the body from accumulating reproducing too many damaged cells, that have accumulated damage throughout their lifetime. Once a cell stops replicating and becomes senescent, it can either undergo programmed cell death–apoptosis–or linger in the tissue. This is where senescence stops working in our favor. Senescent cells emit inflammatory factors as a way to signal our immune system to clear them away. But when our immune system can’t keep up, these factors induce chronic inflammation, accelerate the aging process, and promote the onset of diseases. For example:

  • Senescent cells have an increased level of reactive oxygen species (ROS)–a free radical that is toxic to the skin and plays a major role in skin aging.5
  • Senescence can produce inflammatory signals that suppress the immune system, which can drive tissue degeneration and certain age-related diseases, including the production of cancer cells.6
  • Senescence can induce a harmful state of “senescence-associated secretory phenotype (SASP)”, which turns senescent fibroblasts into proinflammatory cells that can promote tumor progression.

05What is the impact of senescence on healthy cells?

Senescent cells that are not cleared away by our bodies are like zombie cells: not quite alive, but still creating chaos for the living cells around them. These zombie cells exude pro-inflammatory factors and other chemical signals that induce senescence in healthy neighboring cells–setting the stage for chronic disease. To make matters worse, senescent cells can also drive immune cells into senescence, reducing the overall number of immune cells available to fight pathogens and other damaging stimuli.7 As a result, senescent cells are one of the main drivers of biological aging and age-related diseases, such as cancer, Alzheimer’s, Parkinson’s disease, diabetes, osteoporosis, osteoarthritis, and cardiovascular diseases.2

06What is the relationship between cell senescence and aging?

When we are young, our bodies efficiently remove senescent cells in order to make room for young and healthy cells. However, as we age, not only do we produce more senescent cells, but our bodies also lose the ability to clear out 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).

beta-galactosidase staining used to identify senescent cells

07How is senescence linked to skin aging?

Increasing levels of senescent cells in our skin weakens our skin barrier. Once the skin barrier is compromised, a cycle called inflamm-aging begins. Inflamm-aging is senescence-triggered inflammation that spreads across the body. When senescent cells are left to linger in tissues, this inflammation can trigger both aesthetic aging–wrinkles, dead skin cell accumulation and loss of firmness–and age-related conditions like a higher risk of skin cancer.

08Is it possible to slow down cellular senescence?

Wondering how to get rid of senescent cells? Here’s the good news. Scientists have discovered that eliminating and preventing senescent cells is not only possible, but an effective way to slow aging. Specifically, many current longevity studies are exploring senotherapeutic molecules that eliminate senescent cells as a way of extending lifespan and healthspan. Early research has shown that eliminating senescent cells in model organisms, such as rodents, can reduce systemic levels of inflammation and extend immune function. This in turn delays the onset of age-related diseases, effectively extending the lifespan of the organism. With these initial studies as a guide, senotherapeutic treatments are now being studied for applications across osteoarthritis, kidney disease, cardiovascular disease, and many other old age-related disorders.10, 11

09OneSkin’s OS-01 peptide reduces cellular senescence

Here at OneSkin, our team of scientists have discovered a proprietary senotherapeutic peptide, OS-01, that reduces the number of senescent cells in in vitro skin cultures – thereby slowing skin aging and reducing the skin’s biological age (Zonari, et al).

How do we know? When compared to healthy cells, senescent cells show high activity of an enzyme called beta galactosidase. By applying this enzyme’s substrate, called X-gal, to skin cells, we can selectively stain senescent cells blue. This makes it possible to identify and count the number of senescent cells in a skin model. We also utilize expression analyses for several senescence-related markers to measure the level of cellular senescence in skin. By comparing the number of senescent cells before and after topical treatment with the OS-01 peptide or any other molecule/product, we can quantify the treatment’s ability to reduce cellular senescence.

In our tests, the OS-01 peptide reduced the number of senescent cells in in vitro skin cultures by up to 50% while maintaining the total number of cells, meaning it promoted not just the reduction of senescent cells, but also the renewal of healthier ones (Zonari, et al).

Recent innovation in the skin care industry has fallen short of the advances in longevity science. But at OneSkin, we put next-generation science directly into your hands with our OS-01 peptide, to prevent accumulation of senescent cells and extend the health of your skin.

10Key Takeaways

  1. Cellular senescence is one of the nine hallmarks of aging and occurs when a cell reaches the end of its life cycle and stops dividing.
  2. The three types of senescence are replicative senescence, oncogene-induced senescence, and stress-induced senescence.
  3. Though senescence is an evolutionarily protective measure against the proliferation of unhealthy cells, senescent cells can cause widespread damage if left to linger in tissues.
  4. Senescence is linked to several age-related diseases and can cause systemic inflammation, along with visible signs of aging.
  5. Senotherapeutic compounds, which target senescent cells, are making their way to the forefront of longevity research as a way to extend healthspan.
  6. OneSkin’s proprietary OS-01 peptide has been scientifically proven to reduce the number of senescent cells in in vitro skin cultures by up to 50%, powering its ability to reduce skin’s biological age (Zonari, et al).


Sources:

  1. https://www.nature.com/articles/35036093
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344376/
  3. https://www.frontiersin.org/articles/10.3389/fcell.2020.00364/full
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214092/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496685/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496685/
  7. https://www.nature.com/articles/s41586-021-03547-7
  8. https://pubmed.ncbi.nlm.nih.gov/7568133/
  9. https://www.nature.com/articles/s41574-018-0059-4
  10. https://pubmed.ncbi.nlm.nih.gov/30616998/
  11. https://pubmed.ncbi.nlm.nih.gov/34699859/
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