What are Zombie Cells & How Can We Remove Them?








Reference Lab

APRIL 25, 2022


Senescent cells, otherwise known as “zombie cells”, are developed through the process of cellular senescence. Ever since cellular senescence was defined as one of the nine hallmarks of aging, scientists have discovered that eliminating senescent cells, or zombie cells, from tissues could be an effective way to reverse aging in the skin and body. But first, what exactly are these zombie cells, and why do they have such an ominous name?

What are zombie cells?

When cells become old or damaged, they stop replicating and enter a phase referred to as cell senescence. In the body’s most efficient state, these old and damaged cells should undergo apoptosis (cell suicide), but unfortunately, some of them refuse to die, rendering them senescent, or zombie, cells. As the name suggests, these cells can wreak havoc on the surrounding cells and tissues.

Are zombie cells different from senescent cells?

No, zombie cells are a term coined to describe senescent cells. They are one in the same.

Where do zombie cells come from?

The biological purpose of cellular senescence is to prevent further replication after a cell experiences excessive DNA damage. Here are three main varieties of senescence, each with their own causes.1
  1. 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.
  2. 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.
  3. Stress Induced - Different stressors, such as oxidizing agents and free radicals, can cause single stranded breaks (SSBs) in DNA. They actuate a DNA damage response, which then triggers a signaling pathway, prematurely sending healthy cells into senescence.2
Another stressor which can damage DNA is UV radiation. Radiation ionizes the DNA nucleotides and is a serious source of double strand breaks (DSBs), the most dangerous kind of DNA damage. UV exposure from the sun is the main reason we see substantial numbers of zombie cells in our skin. 3

How do zombie cells work?

Zombie cells want to get caught. The entire purpose of the senescence state is not only to prevent further cell replication, but also to alert the immune system to clear the zombie cells out. They attempt to communicate with the immune system by excreting inflammatory factors and utilizing cellular signaling. Ideally, the body reacts by sending inflammatory cells to the area to clear them out. Unfortunately, as our immune system weakens and becomes less diligent with age, these two initially helpful systems can backfire and accelerate aging.
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How does the build up of zombie cells play a part in aging?

The build up of zombie cells accelerate aging primarily as a result of two factors: chronic inflammation and stem cell exhaustion.4


Inflammation

As the immune system becomes less efficient at clearing away zombie cells, they are left to linger and secrete harmful factors, resulting in chronic inflammation.3 Chronic inflammation is when there is excess of these inflammatory cells in the body. This can lead to clots throughout the bloodstream, and the brain vessels. Inflammatory cells also encourage tumors and neurological disorders, by increasing cellular proliferation and resistance to cell suicide. Overall, chronic inflammation has a hand in several age-related diseases including Alzheimer's, heart disease, cancer and diabetes.5


Stem Cell Exhaustion

As the immune system weakens, the cellular signaling from zombie cells starts to land on deaf ears. As a result, they are not cleared away in time and instead, the signaling starts to influence neighboring cells towards senescence. Impressionable stem cells are especially affected by this and often become damaged, or fall into senescence. Senescent cells are also able to disrupt the joint network of these cells; this impedes cellular communication, structural integrity, cell growth, etc. Through these means, zombie cells are able to interfere with stem cell function and growth and disrupt the overall balance of a tissue. Stem cell exhaustion is a crucial contributor towards the aging process, and can eventually lead to organ dysfunction.2

What do zombie cells mean for your skin health?

Being our most exposed organ, our skin experiences a lot of DNA damage from UV exposure. Sun damaged skin leads to stress-induced senescence, activating the DNA damage response, and prematurely sending our cells into senescence. This accumulation of senescent cells in the skin leads to a weakened skin barrier, which can cause visible signs of aging, such as sagging and wrinkles, an accumulation of dead skin cells on the face and body, and compromises your body’s ability to protect itself from external stressors. These cells can also travel to the rest of the body, and can have drastic implications on overall health.

Can you get rid of zombie cells?

Luckily, there is a class of molecules, called “senotherapeutics”, with the ability to prevent the accumulation of and clear away zombie cells by inducing apoptosis (cell suicide). This class of molecules has shown promising effects on preventing and reversing the aging process by reducing senescent burden in the body. In fact, a 2019 study determined that senotherapeutic molecules are able to ease, and occasionally reverse, several age-related illnesses, including Alzheimer’s disease!6Senotherapeutic molecules have shown great potential in the longevity sciences, but how about their specific implications on long term skin care?

OS-01 as a senotherapeutic molecule

The OS-01 peptide is not just any senotherapeutic molecule, it’s a highly effective one designed for optimal penetration in the skin when applied topically. To discover OS-01, the OneSkin team studied 800 promising senotherapeutic peptides in the lab, evaluating each peptide’s ability to reduce cellular senescence. Of all tested peptides, the OS-01 peptide was found to be most effective at clearing zombie cells in skin, reducing the number of senescent cells by up to 50% in human skin models. In fact, by reducing senscent burden in skin, the OS-01 peptide also reduced the skin’s biological age by 2.5 years, after only 5 days of exposure!

Key Takeaways

  1. The biological purpose of cellular senescence is to prevent further replication after a cell experiences excessive DNA damage. DNA damage response pathways, or tumor suppressant pathways can prematurely create a zombie cell.
  2. Zombie cells excrete inflammatory factors and employ cellular signaling to alert the immune system to clear them out. When immune function experiences age-related decline, these senescent attributes can lead to chronic inflammation and stem cell exhaustion.
  3. The accumulation of senescent cells in the skin leads to a weakened skin barrier, which can cause visible signs of aging, such as sagging and wrinkles, and compromise your overall health.
  4. Senotherapeutic molecules have shown promising effects on preventing and reversing aging by reducing senescent burden in the body.
  5. The OS-01 peptide is a highly effective senotherapeutic molecule designed for optimal skin penetration when applied topically. Whether you opt for a peptide moisturizer for your face or body lotion with peptides, the ingredients used in our topical supplements are formulated to repair and protect the healthy cells in our skin.

By Kiran Kumar: Kiran is studying Biotechnology Engineering at UC San Diego. She is highly enthusiastic about longevity sciences, specifically reproductive aging! You can find more on her at thisiskirank.com.


Sources:

  1. https://www.frontiersin.org/articles/10.3389/fcell.2020.00364/full
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214092/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763322/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748990/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704802/
  6. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(18)30629-7/fulltext

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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