Want to know something amazing?
The cells of your body contain all that is needed to keep your muscles, bones, organs, and even the brain optimally functioning. To manage it all efficiently, they replicate and divide into new, healthier cells that can continue maintaining bodily function and repair processes.
Cell division is broken down into several phases, each of which serve an important purpose. You may remember this from high school biology. Let’s take a trip down memory lane and cover the basics of cell division. The main question we should be asking ourselves is…how and why does it impact cellular function and in turn, our overall health?
Back to the basics
Long story short: cellular division keeps the body young. It’s the process by which cells replicate their genetic information (or DNA), split that DNA into two parts, then divide those two DNA partitions into separate “offspring” daughter cells. In turn, these daughter cells repeat the process, replicating and splitting DNA to be shared with their daughter cells, so on and so forth.
In 1961, Hayflick & Moorhead set out to test an interesting question: will cells just continually divide and create new cells, seemingly infinitely?
In one of their experiments, they found that if human fibroblast cells were allowed to grow endlessly in a petri dish, the process of cell division would progressively slow as the cells “aged.”
Eventually, the scientists found that this cell division would stop altogether. Interestingly, this wasn’t the end for these cells…they continued to function by generating energy via mitochondria and synthesizing the proteins necessary to maintain their cellular activity.
As cell division is typically thought of as a cardinal feature of a “living” cell, this observation became a popular finding. Because these cells would stop dividing, but continue to function like a living cell, they came to be known as “zombie cells.” Much like those bloody menaces from your favorite slasher film, they’re considered to be functioning, but “undead.”
Zombie cells, as it turns out, serve quite an interesting purpose in the human body, and are associated with the process called cellular senescence.
...by experimentally inducing senescence, researchers have found that senescent brain cells play a key role in memory impairment
The wonders of cellular senescence
Senescence, as many concepts in science, was derived from a Latin term known as Senex, which translates to “old man” in Latin.
Typically, the body would want to get rid of cells that have seemingly “lost” some of their natural function, such as cell division. But interestingly, senescent cells completely change their structure and function, and begin to emit anti-death signals (collectively known as the “secretome”) to the surrounding environment. In turn, this allows the senescent cell to avoid destruction by processes like apoptosis and autophagy.
The activation of the secretome releases pro-inflammatory signals into the extracellular environment that not only maintains the senescent cell’s survival, but also signals neighboring cells to undergo the same senescence. That’s right, just like zombies infecting healthy humans in order to add to their zombie ranks. Somewhat of a “cellular apocalypse,” if you will.
Why does senescence occur?
Over time, cells can become continually impacted by things like foreign pathogens, injury, and excessive energy processing (i.e., overeating, high-fat diets, etc.), which can all cause significant stress to the cell.
When cells deal with these stressors, they increase the production of oxidizing compounds, like H2O2 (peroxide) and other reactive oxygen species, or ROS. Accumulation of these compounds can damage DNA and mitochondria within the cell, which can ultimately affect the cell’s function.
At the same time, small, repeated DNA structures that are attached to a cell’s genetic material, known as telomeres, also play a significant role in senescence. Telomeres have been proposed as biogenetic markers of a cell’s age.
Cells begin with “long” telomeres; but, over time, after a cell divides over and over again, its telomeres shorten. And because telomeres provide a protective “coating” on the ends of DNA structures, the loss of telomeres can lead to erosion of DNA and thus, mutation or loss of genetic material.
The thing is, these effects don’t just impact the DNA and mitochondria of the parent cell, but they can also result in changes to DNA that is passed down to daughter cells during replication. This is one of the primary reasons that cells undergo senescence; they don’t want to pass on bad genes to their offspring, so they just stop dividing altogether. However, because they’re still able to carry out basic functions, they don’t die off and continue the basic, necessary maintenance processes in the cell.
Is senescence good or bad for the body?
We know all that talk of zombies makes this seem pretty dangerous, right? But truthfully, senescence can be a good thing. It is essential to halt the division of damaged cells, which can lead to the transfer of mutated DNA (i.e., potentially oncogenic) and faulty cell division.
However, as we age, the accumulation of senescent cells may pose a problem.
Remember that these zombie cells release inflammatory molecules, signaling nearby cells to undergo senescence and fend off the body’s own waste control mechanisms that are trying to destroy the zombie cell altogether.
The problem is, when enough of these cells begin to accumulate, this can be a source of long term, low-grade inflammation in the body. This type of inflammation has been linked to many age-related chronic diseases. So, while some senescent cells are manageable, having too many can become a problem.
Think of it like caring for weeds on your front lawn. You may have bright, healthy grass, but if you notice one or two dandelions, it’s no big deal: your lawn can still flourish with them hanging around. But as the dandelions begin to spread and take up more space, you will probably notice the quality of your grass declining. Those weeds are stealing nutrients that could be better served going to your grass.
To tackle this problem, you go out and buy pesticides to manage the weeds. Once they’re removed, there’s fresh space for new, healthy grass to grow, which will help your lawn return to its original, healthy state. Balanced.
So back to the lesson: the blades of green grass are our healthy cells, and dandelions senescent ones. As these senescent cells accumulate, they take away from the ability of healthy cells to thrive and use up the available nutrients. In the end, the more senescent cells, the less likely healthy cells can continue to divide and flourish in the surrounding environment.
Considering these senescent cells have been linked to various chronic inflammatory disease states, scientists are starting to think about applying this same logic as they investigate ways to remove senescent cells to improve the human healthspan.
How are zombie cells linked to health and bodily function?
So we know how it works, but what does that actually mean for our day to day as humans?
One aspect by which senescence can affect health and bodily function is through immunosenescence. Because immune cells are responsible for clearing out senescent cells in the body, when immune cells themselves become “zombified,” the immune system’s ability to clear our senescent cells weakens. This, in turn, can be dangerous as it gives senescent cells the green light to accumulate in the body.
Age-related complications like frailty, osteoarthritis, cancer, diabetes, and cardiovascular disease have all been related to inflammaging—the gradual increase in systemic inflammation as we age. Given the role of senescence in triggering inflammation, researchers believe that zombie cells can actually trigger the inflammatory mediators responsible for driving many of these ailments.
It’s important to note that zombie cells can even have an impact on the brain. In fact, by experimentally inducing senescence, researchers have found that senescent brain cells, including glial cells (i.e., astrocytes), play a key role in memory impairment. To combat it, they’ve found targeting oxidative stress by supplementing with antioxidants can reverse the impact of senescent cells and restore memory function.
These findings not only highlight the importance of senescence as it relates to brain function and age-related cognitive decline (i.e., development of dementia), but it also introduces the idea that it may be possible to control the impact of senescent cells by using antioxidant compounds.
What can we do about senescent cells?
While research in this area is still in its novelty, senolytics may be the key to reverse some of the problems associated with zombie cells. Senolytics are a classification of drugs designed to destroy and contain senescent cells or to prevent or reverse cellular senescence.
Natural antioxidant compounds like astaxanthin have been shown to reverse the impact of senescent cells on oxidative stress and inflammation in experimental models, which has provided a mechanism as to how senolytics may sever the relationship between senescence and memory impairment.
Another compound known as glutathione (GSH) has also shown promise as an effective senolytic. Many studies have linked declining GSH levels with increased age, and a low level of or altered GSH state has become a key indicator for future Parkinson’s disease.
Importantly, GSH is necessary for cell survival, which makes sense when we consider the many studies that have shown that GSH is a potent antioxidant compound that helps buffer ROS and reduce oxidative stress, both of which can lead to increased inflammation.
While targeting and removing senescent cells may not be necessarily feasible in the very near future, reducing the effects of these cells through approved senolytics and antioxidant compounds like GSH, may be the best way to protect against age-related diseases and improve our healthspan as a whole.
So, we’ll leave you with a little advice. If you find yourself prepping for a zombie apocalypse, you may want to consider packing some antioxidants with you.