They can destroy joints, the heart, bones, and skin, and promote accelerated aging.
Who would have thought that aging research, geroscience, and longevity science would involve zombies?
Zombies in our bodies wreaking havoc on pretty much all of our tissues, making us age in an almost exponential fashion?
- Who are these zombies and where did they come from?
- How do we stop them?
- Do we want to stop them? Are they the cause of inflammation or are they trying to save us?
- Maybe zombies have good intentions but are being targeted as villains…
What are Zombie Cells?
‘Zombie cells’ is a catchy nickname for senescent cells. They typically are older cells that have stopped functioning properly.
When most cells become old, damaged, or potentially dangerous, they:
- Repair themselves
- Die and get cleared away (apoptosis)
A senescent (aka Zombie) won’t die or repair itself. Instead, it takes on a different role:
- It stops dividing (this is a good thing; we will circle back to)
- Sticks around in your tissues
- It starts acting SASP-y (secreting lots of inflammatory markers)
SASP stands for Senescence-Associated Secretory Phenotype
SASP is basically a fancy term describing when a cell becomes a zombie and starts a big commotion, a serious scene.
The zombie cell begins releasing inflammatory markers, triggering inflammation, damaging nearby healthy cells, and interfering with tissue repair.
Because these zombie cells can be anywhere in your body, this is where you see:
- Accelerated aging
- Inflammaging (inflammation + aging = inflammaging)
- Osteoarthritis
- Cardiovascular disease
- Insulin resistance
- Fatty liver disease
- Neurodegenerative conditions
What Causes Zombie Cells?
‘Doctor, she was such a nice cell. Got along well with others, cooperative, dependable, agreeable, and never missed a division. She worked so well with others in her tissue-class. We never saw this coming. Now she is loud and dramatic, spouting so much inflammation. She is affecting the other cells around her. We never saw this coming.’
How does your happy, well-adjusted, healthy cell turn into a loud, obnoxious, chaotic, troublemaker Zombie!?
Triggers to provoke your happy cell into an angry, inflammatory, spewing zombie:
- DNA damage
- Oxidative stress
- Chronic inflammation
- Smoking
- Visceral adipose fat tissue
- Radiation
- Aging
- Environmental toxins
- Mitochondrial dysfunction
Don’t Shoot the Messenger:
The Zombies really just want to help you. They are the heroes disguised as villains.
Imagine a cell becomes damaged, maybe:
- DNA is damaged, it's been exposed to toxins, it's older, and has divided too many times, or is at risk of becoming cancerous.
Your body has some choices to make:
- Option A: Let the cell keep dividing and risk cancer (NO!)
- Option B: Kill through apoptosis
- Option C: Put the cell under permanent house arrest (no more dividing)
The body would love and much prefer option B. Kill the damaged cell and be done with it.
But as we all know, life is not that simple.
Zombie cells have a purpose. It’s when the purpose goes awry that we see destruction. This will become more clear soon enough.
Back option C: If the cell cannot undergo apoptosis (cell death), then it becomes a senescent cell.
One of the main drivers is to prevent the cell from continuing to divide and becoming cancerous. The alternative to a cancer cell (that is continuously dividing) is a zombie cell (an inflammatory loudmouth).
Plot Twist: Who Needs a Hero?
We've been blaming the wrong character.
Zombie cells weren't created to hurt us. They were created not only to protect us from cancer risk, but zombie cells were also created as a cry for HELP.
‘Help, Help, Mayday! Anyone listening?
Requesting immediate assistance, do you copy??
We have DNA damage! I repeat, we have DNA damage.
Send tissue repair! I need immune system backup!
This is not a drill!
Evacuate the wounded!
And somebody airlift me outta here and get me a one-way ticket to apoptosis!’
Zombie cells are sending out distress signals.
They are saying:
- I’m damaged. Come remove me
- There is a need for tissue repair and wound healing
Who’s Listening? Who is the Zombie cell calling for?
Who are the first responders that the Zombie cell is radioing?
-
Immune system AKA The Cleanup Crew
- Natural killer (NK) cells: Take out the damaged cell
- Macrophages: Clean up the mess/debris
- T-cells (CD4+ and CD8): Coordinate and eliminate the zombie
- Neutrophils: the very early responders to an acute injury
-
Tissue Repair/Remodel Team:
- Fibroblasts: build, close, repair, remodel
- Endothelial cells help build new vessels
-
The Replacements:
- Stem cells are your body's replacement cells, waiting in the wings to become whatever new healthy cell is needed
-
The Dispatchers:
- Cytokines and chemokines send out emergency signals that recruit and direct immune cells, increase blood flow, and coordinate tissue repair.
Zombie cells are not the problem.
In fact, if humans couldn't make senescent cells, we'd probably have more cancer, poorer wound healing, and impaired tissue repair.
The problem is persistence.
As we age, zombie cells are allowed to stay ‘too long.’
A zombie cell that hangs around for a few days can help with healing. But one that persists or sticks around for a long time becomes an inflammatory problem that can promote age-related conditions like:
- Heart disease
- Arthritis
- Osteoporosis
- Muscle loss
- Type 2 diabetes
- Cognitive decline and dementia
- Slower wound healing
- Increased risk of some cancers
What’s the Problem Then?
Let’s back up and look at the big picture.
In youth, our ‘Rescue Team’’ works pretty well:
- The cell becomes damaged
- The cell enters senescence and sends out distress signals
- The immune system responds and recognizes the issue/damage
- The immune system removes the zombie cell and repairs the damage
Problem solved.
So why doesn’t this keep happening as we age?
The honest answer is: we don’t completely understand/know. That is why so much more research is underway to better understand aging.
Some thoughts on why the system becomes less efficient as we age:
- As our immune system ages (immunosenescence), the very cells responsible for recognizing and removing senescent cells become fewer in number, slower to respond, and less efficient at doing their job.
- The workload increases. Decades of DNA damage, oxidative stress, infections, toxins, and everyday wear and tear create more senescent cells than the aging immune system can easily keep up with.
- Senescent cells appear to become surprisingly good at surviving. They activate "pro-survival" pathways that help them resist being eliminated, almost as if they barricade themselves inside and refuse to leave. Maybe not all zombie cells are as benevolent or self-sacrificing as I alluded to: ‘I want more life, father’ - Roy Batty.
- Aging tissues change. Blood flow, intercellular communication, and the local tissue environment all become less efficient, making it harder for immune cells to reach the site and complete the cleanup.
The result? The senescent cell continues broadcasting inflammatory distress signals that were originally meant to be temporary.
Instead of lasting just long enough to coordinate repair, those signals can persist, contributing to chronic, low-grade inflammation (inflammaging). Inflammation leads to degeneration, hence age-related chronic conditions.
Ironically, the problem isn't that our bodies developed senescent cells.
The problem is that the cleanup crew gradually loses its ability to escort them off the stage.
In other words, the emergency response system doesn't completely stop working. It simply becomes less efficient, allowing more senescent cells to accumulate over time with continued inflammation.
What Can We Do?
Now we know the goal is not to prevent the production of zombie (senescent) cells. Remember, zombie cells are part of your body's natural emergency response. They help protect against cancer, coordinate tissue repair, and call for help when something is wrong.
The goal is to prevent zombie cells from overstaying their welcome.
The goal is to reduce inflammation (inflammaging) by:
-
Improve Cleanup:
- Support the immune system so it can more efficiently recognize and remove zombie cells.
-
Remove Persistent Zombies:
- Help the body clear persistent zombie cells after they've completed their job.
-
Quiet Inflammatory Signaling:
- Reduce the chronic inflammatory signals (inflammaging) produced by zombie cells that stick around too long.
-
Create An Environment With Fewer Zombies:
- Reduce the damage that creates excess zombie cells in the first place (oxidative stress, smoking, obesity, chronic inflammation, etc.).
Zombie (senescent) cells are one hallmark of aging, not the entire aging process. But they can amplify the aging process. Understanding them (bc I love the science-y part), we can then figure out strategies to help us support the body’s natural ability to repair, clean up, and maintain itself over time.
In the paid newsletter, we'll explore each of these strategies and what interventions appear most promising.
