Zombie Cells: Everything You Need To Know

What are Zombie Cells?

Zombie cells are damaged cells that have stopped dividing but refuse to die, also known as senescent cells. Senescence is a stress response characterized by the production of chemical mediators that influence tissue health. Senescent cells that resist elimination by the immune system linger in tissues and gradually accumulate, promoting tissue dysfunction, unhealthy aging, and age-related health decline [1,2]. 

Cells become senescent in response to different types of stress, ranging from environmental insults to mitochondrial dysfunction, DNA damage, oxidative stress, or telomere shortening, among others. Despite accumulating damage, they linger (akin to how Zombies refuse to die in books, TV shows, and movies) by upregulating pro-survival and downregulating pro-apoptotic pathways, allowing them to remain in tissues indefinitely [3–5]. 

What Is Cellular Senescence?

Senescence is a stress response that occurs as part of healthy tissue function. In normal conditions, senescent cells exert tissue-protective actions and are quickly eliminated by the immune system. But with aging, as immune clearance becomes less effective, senescent cells accumulate and contribute to age-related tissue dysfunction and health decline [6].

Senescence is characterized by a permanent state of growth arrest and the production of chemical mediators collectively known as senescence-associated secretory profile (SASP). SASP mediators include cytokines, chemokines, matrix metalloproteinases, and other bioactive molecules that influence tissue health and immune function [1,2].

How Does Senescence Affect Health?

Senescent cells can have beneficial or detrimental effects [4,7]. Transient senescence is beneficial because it’s part of a protective response that suppresses the proliferation of dysfunctional cells. Transient senescent cells also promote tissue repair and regeneration, contribute to tissue homeostasis, and recruit immune cells that remove other damaged cells [3]. 

However, these benefits rely on the transience of senescence. In normal conditions, SASP mediators recruit immune cells that eliminate senescent cells, making their action self-contained and allowing a beneficial outcome. But when their clearance fails, either due to immune inefficiency or senescent cell ‘camouflage’, senescent cells linger in tissues and senescence becomes detrimental. Lingering senescent cells can be damaging because they accumulate and carry on secreting SASP molecules whose actions were meant to be short-term [1–3]. 

SASP molecules influence physiological signaling pathways that can lead to tissue damage, disruption of immune function and signaling, and tissue health deterioration [1–3]. SASP mediators can also induce senescence in neighboring cells, creating a snowball effect of senescence build-up, tissue degeneration, and functional decline [8]. 

The ability of lingering senescent cells to induce senescence in neighboring cells is another part of the reason they are referred to as zombie cells.

The ability of lingering senescent cells to induce senescence in neighboring cells is another part of the reason they are referred to as zombie cells. Just like zombies that turn healthy people into zombies, senescent cells can change healthy cells into more senescent cells. 

Zombie Cells in Aging

Senescence is one of the hallmarks of aging [9]. The number of zombie cells in the body increases with age and the rate of senescent cell accumulation accelerates with aging. Senescent cells contribute to aging and poorer health as we age [10,11]. 

The number of zombie cells in the body increases with age and the rate of senescent cell accumulation accelerates with aging.

The accumulation of senescent cells with age can result from an increase in senescence due to the combined effects of different senescence-inducing stressors acting simultaneously, as various cellular stressors that induce senescence increase with aging. With aging, the immune system also becomes less efficient at finding and clearing senescent cells, creating an opportunity for transient senescent cells to evade elimination and linger [5,6]. 

When senescent cells accumulate in tissues in sufficient numbers, they may actively drive a cascade of senescence, interfere with tissue repair and regeneration, and increasingly promote tissue dysfunction and unhealthy aging [3]. All cell types can undergo senescence during aging, even those in non-proliferating or slowly proliferating tissues, such as the brain or the heart [12–14].

How Can Zombie Cells Be Cleared?

Senescent cells can be modulated in three main ways: (1) selective elimination of senescent cells using senolytics; (2) SASP neutralization using senomorphics; and (3) enhancement of immune-mediated senescent cell clearance [15]. 

Senolytics are substances that preferentially target senescent cells and support the body in protecting itself against senescent cell burden. Senolytics have an affinity for finding senescent cells, counteract their pro-survival and anti-apoptotic mechanisms, and drive them into cell death by apoptosis. The advantage of senolytics is that they target the root cause and permanently remove senescent cells [16], abolishing the production of deleterious SASP as a consequence. Studies in animals have shown that the selective elimination of senescent cells with senolytics enhances healthspan and longevity [17–20].

Senomorphics neutralize the SASP by blocking signaling cascades within senescent cells, disrupting secretion of the SASP, or inhibiting the activity of individual SASP mediators. However, senescent cells of different origins secrete different SASP factors and drive tissue dysfunction through varying mechanisms, making this approach more complex [15]. 

Senescent cells from different tissues are also driven into apoptosis through distinct senolytic mechanisms [2]. Therefore, senolytics with different tissue selectivities may be combined to provide a more comprehensive intervention that targets different types of senescent cells with different SASPs. 

Promoting immune health and the efficiency of immune clearance of senescent cells helps to support the body’s natural processes of senescent cell elimination and to restore the balance between senescent cell generation and clearance [15].

How Can Qualia Senolytic Help Manage Zombie Cells?

The main goal of Qualia Senolytic is to support healthy aging by helping to bring the creation and clearance of senescent cells back into a healthy balance. Qualia Senolytic was also designed to support the efficient use of cellular resources, encourage the growth of more youthful cells by removing senescent cells, support tissue health, and revitalize aging tissues, promoting whole-body rejuvenation.*

Qualia Senolytic combines senolytic ingredients with different tissue affinities, providing a more comprehensive approach to senescent cell management.* All nine ingredients in Qualia Senolytic have shown senolytic potential in preclinical research by promoting the apoptosis of senescent cells or their immune clearance.* Some are even being used in ongoing clinical trials, namely quercetin and fisetin. 

Learn more about Qualia Senolytic in The Formulator's View of the Qualia Senolytic Ingredients.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

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