September is Healthy Aging Month. And this year I want to use it to talk about something that is happening inside every one of our bodies right now—something the scientific community has been studying intensively for the past decade—that most people have never heard of in plain language.
Zombie cells.
That is not a metaphor I made up. That is the actual nickname that researchers use, and it fits perfectly. Once you understand what these cells are and what they do to your body over time, the logic of why we work so hard on longevity medicine becomes very clear. And so does the science behind one of the most evidence-supported tools we carry at TREVI: ProLon.
What Are Zombie Cells—and Why Should You Care?
Let's start with the basics. Every cell in your body has a life cycle. It grows, it does its job, and eventually it gets old or damaged. When that happens, the cell is supposed to either repair itself or die in an orderly way—a process called apoptosis—so that new, healthy cells can take its place. Think of it like the natural turnover of any well-run system.
But here is where it goes wrong.
Some cells, as they age or sustain damage, reach a point where they can no longer function properly—but they also refuse to die. They go into a kind of suspended state. They stop dividing. They stop doing their original job. Scientists call this state cellular senescence—and they call these cells senescent cells, or more memorably, zombie cells.
Zombie cells are not inert. That is the critical point. Even though they are no longer functional, they are actively harmful. They release a continuous stream of inflammatory chemicals into the surrounding tissue—a pattern researchers have named the Senescence-Associated Secretory Phenotype, or SASP. This inflammatory signal damages healthy neighboring cells, disrupts tissue function, impairs organ repair, and—over years—contributes to virtually every condition associated with aging.
Joint pain and stiffness. Cardiovascular disease. Cognitive decline. Metabolic dysfunction. Skin thinning and loss of elasticity. Immune system aging. The accumulation of zombie cells has been implicated in all of them.
Why Does This Happen More as We Get Older?
Your immune system is actually your first line of defense against senescent cells. Specialized immune cells are designed to seek them out and clear them. When you are young and your immune system is functioning well, this clearance keeps pace with accumulation. But as the immune system itself ages—a process called immunosenescence—it becomes less efficient at identifying and removing zombie cells. They accumulate. The inflammatory burden grows. And the downstream effects compound over time.
This is why senolytics—interventions designed to selectively eliminate senescent cells—have become one of the most actively studied areas in longevity medicine. Pharmaceutical senolytics are still moving through clinical trials. But you do not have to wait for a drug. One of the most powerful senolytic mechanisms available is one your body already knows how to use. It just needs the right signal.
The Body's Built-In Cleanup System: Autophagy
The word autophagy comes from the Greek for "self-eating." It is exactly what it sounds like. When the body is deprived of nutrients for a sufficient period, cells activate an internal recycling program—breaking down damaged components, malfunctioning proteins, and yes, senescent cells—and either re-purposing the parts or clearing them out entirely.
Autophagy is always running at a low level. But it ramps up significantly in response to fasting. This is one of the reasons caloric restriction and fasting have been associated with longevity across species from yeast to mice to primates. The cleanup signal gets louder when energy is scarce.
For a long time, this was well-established in animal models but difficult to study directly in humans. That changed in December 2025, when the first clinical trial to directly measure autophagy in humans during a dietary intervention[2] was published. Thirty healthy adults were randomized to receive either a five-day Fasting Mimicking Diet (ProLon), a similar fasting-mimicking formulation, or a control diet. The ProLon group showed a measurable increase in autophagy flux—the actual rate of cellular cleanup—confirmed through blood samples collected during and after the intervention.
This matters because it is direct human evidence of the mechanism—not an inference from animal data or a theoretical extrapolation. ProLon demonstrably activates the cleanup process in real human cells.
The Rebuild: What Happens When You Refeed
This is the part of the ProLon story that genuinely surprised me the first time I read it—and it is the piece that separates fasting-mimicking from other longevity protocols.
During the five days of the ProLon program, the body enters a state of nutritional stress. White blood cell counts drop as the immune system begins breaking down old and damaged immune cells—a process called apoptosis of the aged cells. This sounds alarming until you understand what happens next.
When you begin eating again—re-feeding—the body reads that drop in white blood cells as a signal that something needs to be rebuilt. Dormant repair processes switch on, and the immune system is replenished with fresh, newly generated cells rather than the old ones that were cleared out.
Dr. Valter Longo's lab at USC demonstrated this in a 2014 paper published in Cell Stem Cell[3]: prolonged fasting cycles caused a reduction in circulating white blood cells, followed by a rebuilding of the immune system with new cells. The effect was observed in both mice and in early human data. What his team saw was, in essence, the body using the fasting window to dispose of old immune cells and the refeeding window to rebuild with new ones.
Precision matters here. The new cells are not created from nothing—the body draws on its own reserve capacity to replace what fasting helped clear out. The fasting creates the space; the refeeding triggers the rebuild. Together, they constitute a renewal cycle that the body is designed to perform but rarely gets the signal to execute in modern life.
What the ProLon Research Actually Shows
ProLon is not a wellness product with a few small studies behind it. It was developed over 25 years at the USC Longevity Institute under Dr. Valter Longo, with funding from the National Institutes of Health, and has now been tested in 32 clinical trials at 18 institutions including Stanford, Mayo Clinic, and the University of Miami[5]. The evidence base is genuinely substantial.
Here is what three cycles of ProLon—five days per month for three consecutive months—have been shown to do in peer-reviewed published research:
Biological Age Reduction
A 2024 study published in Nature Communications[1], analyzing data from two randomized clinical trials, found that three FMD cycles were associated with a 2.5-year reduction in biological age—measured using a validated biomarker model built from data on more than 10,000 adults. This was not a self-reported "feeling younger." It was a measurable shift in biological markers predictive of morbidity and mortality. The finding held across both of the randomized trials analyzed.
Metabolic and Cardiovascular Improvements
- Reduced insulin resistance, particularly in pre-diabetic participants[4]
- Lower fasting glucose and HbA1c
- Decreased visceral fat (the metabolically active fat linked to cardiovascular and metabolic disease)
- Reduced blood pressure
- Lower CRP—a marker of systemic inflammation—from 1.5 to 1.0 mg/L after three cycles[4]
- Decreased IGF-1, a hormone linked to accelerated aging
Immune System Rejuvenation
Three FMD cycles shifted the lymphoid-to-myeloid ratio—a key marker of immune system age—back toward a more youthful state. As mentioned above, the pattern of immune cell clearance and rebuilding mirrors what Longo's lab originally observed in prolonged fasting, now achieved through a structured, food-based protocol.
Autophagy Activation
The December 2025 autophagy trial[2] confirmed measurable increases in cellular cleanup activity during the ProLon protocol—the first direct human evidence of this mechanism, previously established only in animal models.
The Plain-Language Summary
Here is how I explain it to patients in the office:
Your body has a natural maintenance program. It is designed to periodically clear out old, damaged, and dysfunctional cells and replace them with new ones. When this system runs well, you age more slowly. When it runs poorly—because of constant eating, chronic stress, poor sleep, and a lifestyle that never gives your cells a recovery window—old cells accumulate, inflammation builds, and the downstream effects show up as every symptom we associate with aging.
ProLon gives your body a five-day window to run that maintenance program. You are not starving—you are eating carefully calibrated, plant-based nutrition that keeps you fueled while sending your cells the biological signal that triggers cleanup and regeneration. Then you eat normally for the rest of the month. Three cycles appears to be the threshold where the measurable longevity benefits show up in the data.
It is five days a month. Most people find it manageable. The discomfort is real but modest and temporary. The results are backed by some of the most rigorous nutrition science published in the past decade.
Who Should—and Should Not—Consider ProLon
ProLon is not appropriate for everyone, and I want to be clear about that.
It is a good candidate for most healthy adults over 30 who want to address biological aging, reduce metabolic risk, improve body composition, or support cellular health. It is particularly relevant if you are dealing with insulin resistance, elevated inflammatory markers, metabolic syndrome, or simply want a structured longevity intervention with a strong evidence base.
It is not appropriate if you are pregnant or breastfeeding, have a history of eating disorders, are significantly underweight, have diabetes requiring medication management (the dietary changes affect blood sugar meaningfully), or have certain other medical conditions. I review all of these individually.
If you are a current TREVI patient and you want to incorporate ProLon into your protocol, come in and let's look at your labs first. The program is most powerful when it is part of a broader plan—not something you add on in isolation.
How to Get Started
You can order ProLon directly through the TREVI ProLon microsite at any time.
For patients who are ready to commit to the full three-cycle protocol, we are offering an in-office preorder at 25% off. To take advantage of this pricing, you will need to choose your preferred ProLon variant, order all three months upfront, and prepay. This is not a casual add-on offer—it is designed for patients who are genuinely committed to doing the protocol as the research intends it.
Not sure where to start? Schedule a consultation and we will review your current labs, health history, and goals to determine whether ProLon is the right fit—and if so, which protocol makes the most sense for you.
Until next month,
Dr. Josie
References
- Brandhorst S, Levine ME, Wei M, et al. Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nature Communications, 2024;15:1309. nature.com
- Espinoza SE, et al. Effect of fasting-mimicking diet on markers of autophagy and metabolic health in human subjects. GeroScience, 2025. Funded by L-Nutra, the maker of ProLon; the company did not participate in data collection, analysis, or interpretation. doi.org
- Cheng CW, Adams GB, Perin L, et al. Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression. Cell Stem Cell, 2014;14(6):810–823. cell.com
- Wei M, Brandhorst S, Shelehchi M, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Science Translational Medicine, 2017;9(377):eaai8700. science.org
- ProLon Science Overview. L-Nutra / USC Longevity Institute—manufacturer's summary of the clinical program (32 trials, 18 institutions). prolonlife.com
