What Is Senescence & Its Relationship To Aging?








Reference Lab

MAY 11, 2022


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 the aging process down?

Skin longevity and aging scientists have, and they’ve discovered some very good news. One of the primary processes behind biological 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 healthspan. Keep reading to learn more about what cellular senescence is, how it’s related to aging, and how it can be reversed.

01What is senescence at a cellular level?

Cellular senescence is one of the nine hallmarks of aging.

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 and in our skin. When we’re young and healthy, senescent skin cells are quickly cleared away and replaced with 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 and accelerate aging in neighboring cells. These signals can even inhibit epidermal stem cell function, decreasing your skin’s 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 our skin function like older skin. When skin acts older, it’s no surprise that it looks older too1.

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 induced in response to internal triggers or environmental stressors, such as DNA damage or oncogenic (cancer-inducing) stress.2

03What are the different types of cell senescence?

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

  • Replicative - This occurs when a cell has hit its maximum number of cell divisions and should no longer replicate. This is the classic senescing process.
  • Oncogene Induced - Oncogenes are genes responsible for cell replication. When these genes are activated, or overexpressed, they allow for higher levels of cell proliferation than optimal. To prevent a tumor, the cell activates two tumor suppressing pathways; these pathways also stimulate cellular senescence.
  • Stress Induced - Different stressors, such as oxidizing agents and free radicals, can cause single stranded breaks (SSBs) in DNA. Cells actuate a DNA damage response, which then triggers a signaling pathway to prematurely send a cell into senescence.4

03Is senescence good or bad?

The purpose of senescence is good, as it is meant to protect the body from reproducing cells that have accumulated too much damage. 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, resulting in zombie cells. And this is where senescence stops working in our favor. Senescent cells that are not cleared away by our bodies emit harmful factors that 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 strong inflammation 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.

04What is the impact of senescence on healthy cells?

Unfortunately, the damage that occurs with senescence 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 neighboring cells. Senescent cells exude pro-inflammatory factors and other chemical signals that induce senescence in healthy neighboring cells. This creates an environment well-suited for the development of chronic diseases. To make matters worse, senescent cells can cause immune cells to enter senescence, thereby reducing the number of immune cells available to fight pathogens and other damaging stimuli. 7As 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).

05What is the relationship between cell senescence and aging?

When we are young, our bodies are more fine-tuned to 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

06What are the biomarkers of senescence?

Identifying senescent cells in tissues or lab cultures relies on a measurement of multiple biomarkers – biological molecules that can be measured and which indicate the state of a tissue or organism. Biomarkers of senescence can be measured via multiple molecular biology tools. There are color staining techniques, such as ‘senescence-associated-β-galactosidase’ 8 which selectively stains senescent cells blue. There are also many immune-mediated inflammatory signals that are turned on and are highly expressed in senescent cells, which can also be measured in the laboratory. OneSkin has utilized these and other methods in our research, and our novel peptide therapy has been shown to effectively reduce the level of these biomarkers in the skin.

07How does cell senescence ultimately impact the health and longevity of skin cells?

An increased level of senescent cells in our skin ultimately weakens our skin barrier and skin health, which leads to both aesthetic aging, such as an increased presence of wrinkles, an accumulation of dead skin cells on the face and body, and age-related conditions, such as a susceptibility to skin cancer.

08How is senescence linked to skin aging?

Once the skin barrier is compromised through an increase in cellular senescence, a cycle called inflamm-aging is initiated. Inflamm-aging is senescence-triggered inflammation that spreads across the body. When senescent cells are 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 diseases9 (Figure 2).

09Is 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 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. This slowing and delaying the onset of age-related diseases effectively extends the lifespan of the organism. Senotherapeutic compounds are now being studied for their application across osteoarthritis, kidney disease, cardiovascular disease, and many other age-related disorders.10, 11

10OneSkin’s OS-01 peptide reduces cellular senescence

Our team of scientists at OneSkin have discovered a proprietary senotherapeutic peptide, OS-01, which can reduce the amount of senescent cells in skin as a way of extending skinspan. Our data shows this as an effective way of slowing skin aging, with the OS-01 peptide being the first molecule proven to reduce skin’s biological age.

11Conclusion

  1. Cellular senescence is one of the nine hallmarks of aging and occurs when a cell reaches its ultimate number of replications and divisions.
  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, it can cause widespread damage if left to linger in tissues.
  4. Senescent cells are linked to several age-related diseases and can cause systemic inflammation, along with visible signs of old age.
  5. Senotherapeutic compounds, which target senescent cells, are making their way to the forefront of longevity research as a way to extend healthspan.

Recent innovation in the skincare industry has fallen short of the advances in aging and longevity science. But at OneSkin, we put next-generation science directly into your hands with our novel anti-aging topical supplement, proven to prevent accumulation of senescent cells in wrinkles. Shop OS-01 Topical Supplement today.


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/

Reviewed by Alessandra Zonari, PhD, Chief Scientific Officer (CSO) and Co-Founder of OneSkin

Alessandra earned her Master’s degree in stem cell biology, and her PhD in skin regeneration and tissue engineering at the Federal University of Minas Gerais in Brazil in collaboration with the 3B’s Research Group in Portugal. Alessandra did a second post-doctoral at the University of Coimbra in Portugal. She is a co-inventor of three patents and has published 20 peer-reviewed papers in scientific journals.

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