With age comes wisdom. But also zombie cells. Never heard of ’em? Scientists call them senescent cells. They linger in our bodies without dying or being replaced. And they can contribute to inflammation, or “inflammaging” as is sometimes said. In this post, we’ll explore what senescent “zombie” cells are, why they are so harmful, and how to use natural senolytics and hormetic stress to get rid of them so you age with more grace and wisdom and less disability and disease.
What Are Senescent Cells and Why Are They Dangerous?
Senescent cells, nicknamed zombie cells, are cells that stop dividing due to aging, DNA damage, or stress. Instead of dying off, they stick around, secreting a toxic mix of inflammatory molecules called the senescence-associated secretory phenotype (SASP). While senescence initially protects against cancer, the buildup of these cells over time can backfire.
The SASP wreaks havoc by:
- Fueling chronic inflammation (inflammaging), linked to diseases like arthritis, heart disease, and Alzheimer’s.
- Disrupting tissue repair and regeneration. They’re basically in the way.
- Creating conditions that, ironically over time, can promote cancer growth.
- Accelerating aging by impairing stem cells and tissue maintenance.
As senescent cells accumulate, they contribute to age-related diseases, including diabetes, cardiovascular issues, and neurodegeneration. Clearing them out is one of the keys to extending your healthspan, that is, the years you live in good health.
What Are Senolytics?
Senolytics (“seno” for senescent and “lytics” for lysis or breaking down and recycling) are compounds that selectively trigger apoptosis (programmed cell death) in senescent cells, leaving healthy cells unharmed. By lightening the load of zombie cells, senolytics aim to lower inflammation, improve tissue function, and delay age-related diseases. Research, mostly in animals, shows exciting results, with human trials now underway.
But, maybe senolytics are just a fancy term for something that has always been with us? Scientists have been studying this specific mechanism of getting rid of old, broken cells, so they gave it a fancy new name. But as you read on, you will see that the same supplements and health practices that have been promoted for health and healing for a long time actually are senolytics. You just didn’t know them by that name before.
Natural Senolytics: Phytochemicals to the Rescue
Certain plant-based compounds, or phytochemicals, act as natural senolytics or senomorphics (which suppress SASP without killing cells). Found in everyday foods, these compounds offer a dietary tool to handle senescent cells, though high doses may be needed for therapeutic effects. Below are the top players, backed by research:
Fisetin
- Found in: Strawberries, apples, persimmons, onions.
- How it works: This flavonoid targets anti-apoptotic pathways in senescent cells, promoting their clearance.
- Evidence: Most potent of 10 flavonoids tested. Stronger effects than quercetin. Administration of fisetin to aged mice restored tissue homeostasis, reduced age-related pathology, and extended lifespan. (Study link)
- Note: Human trials are ongoing, often using intermittent high doses (e.g., 20 mg/kg body weight).
Quercetin
- Found in: Onions, apples, berries, capers.
- How it works: A flavonoid that pairs well with drugs like dasatinib to kill senescent cells.
- Evidence: A 2019 pilot study in EBioMedicine found that quercetin plus dasatinib improved physical function in patients with idiopathic pulmonary fibrosis. (Study link). See more about quercetin in this review.
Curcumin
- Found in: Turmeric.
- How it works: A familiar polyphenol that may reduce SASP and promote senescent cell death via anti-inflammatory pathways.
- Evidence: In an in vitro study curcumin was used to induce senescence in cancer cells. Then the senescent cells were cleared with the use of fisetin and quercitin. (Study link)
- Note: Nutrients work very well in teams, with synergistic effects . Get a premium form of curcumin for the best bioavailability.
Resveratrol
- Found in: Grapes, red wine, and peanuts.
- How it works: Another familiar polyphenol. It acts as a senomorphic (stops the cells from sending out inflammatory chemicals without killing the cells), reducing SASP and boosting autophagy.
- Evidence: A study on osteoporotic rats showed that resveratrol improved bone health through SIRT1 activation and enhanced autophagy. It isn’t clear whether resveratol cleared senescent cells or just enhanced supportive mechanisms. (Study link)
- Note: Less potent than fisetin or quercetin, but resveratrol is renowned for its anti-aging properties through its promotion of SIRT1.
Apigenin
- Found in: Parsley, celery, chamomile.
- How it works: A flavonoid that may suppress SASP and clear senescent cells via antioxidant effects.
- Evidence: In mice with premature aging or prostate cancer xenografts, apigenin improved physical function (e.g., open-field, Y-maze tests), reduced tumor growth, and enhanced chemotherapy efficacy. It lowered SASP factors in serum and tissues of mice, with no significant toxicity observed. (Study link)
- Note: Apigenin is also known for its anti-cancer effects.
Luteolin
- Found in: Celery, green peppers, chamomile.
- How it works: Similar to apigenin, it may reduce SASP and promote senescent cell clearance.
- Evidence: Mice given a daily plant extract from Prawn sage (Salvia haenkei) rich in luteolin have a longer healthspan and lifespan, with specific senomorphic mechanisms slowing down senescence. (Study link)
How to Use Them:
- Diet: Eating foods rich in these compounds (e.g., berries, turmeric, onions) provides low-dose benefits. The team effect may come into effect, whereby several compounds at low doses have an additive, or maybe even a synergistic effect working together.
- Supplements: High-dose supplements are being studied, but optimal dosing and long-term safety aren’t fully clear. Intermittent “hit-and-run” protocols (e.g., a few days every few weeks) are common to minimize risks.
- Caution: Always consult a healthcare provider before starting supplements, as high doses can have side effects or interact with medications.
Hormetic Stress: Strengthening the Body Through Challenge
In addition to eating a plant-based diet that is rich in phytochemicals from whole plant foods like celery, apples, grapes, onions, and peppers, certain lifestyle practices induce what is called hormetic stress, which is a mild stress that triggers repair and resilience, triggering the body to become stronger to resist the stress. This hormetic stress also can clear out senescent, or zombie cells. These lifestyle practices complement the senolytics by boosting autophagy (cellular cleanup) and reducing inflammation. Here are a few of the well-known practices:
Sauna (Heat Stress)
- How it works: Heat therapy does induce stress. As your body’s core temperature rises the heat activates heat shock proteins and sirtuins. This spurs on autophagy and thus, cellular repair. Out with old and in with the new.
- Evidence: A 2015 study in JAMA Internal Medicine linked frequent sauna use (4–7 times/week, 15–20 minutes) to lower inflammation and mortality, possibly by reducing senescence. Men in the Finnish Kuopio Ischemic Heart Disease Study who used sauna 4-7 times a week reduced cardiovascular and all-cause mortality by about 50 percent.
- Try it: Use a Finnish or low-EMF infrared sauna at 65–82°C (150-180°F) for 15–20 minutes at least 4 times a week to get these benefits.
Cold Plunges (Cold Stress)
- How it works: The intense, shocking cold exposure boosts mitochondrial function and reduces inflammation, potentially lowering SASP.
- Evidence: While direct links to senescence are limited, studies like one in Cell Metabolism show cold therapy improves metabolic health, which may indirectly clear zombie cells.
- Try it: Take 1–3-minute cold plunges at 4–13°C (40-55°F). Start gradually at higher temperatures and shorter times initially. You first, then me. 🙂
Exercise and Physical Activity
- How it works: Long known as the ultimate hormetic stress, moderate physical activity induces mild oxidative stress. (Extreme physical activity actually has negative effects.) This can upregulate enzyme-based antioxidants, and also promotes autophagy. That is part of getting fit.
- Evidence: A 2020 study in Aging Cell found exercise reduced senescent cell markers in human and mouse tissues. (Study link)
- Try it: Aim for 150 minutes/week of moderate aerobic exercise and strength training exercises twice a week. If you are short on time, try out high-intensity interval training (HIIT).
Fasting and Fasting-Mimicking Diets (FMD)
- How it works: Caloric restriction triggers autophagy and apoptosis, potentially clearing senescent cells. FMD mimics fasting with a low-calorie, plant-based diet. Our 5-Day Perfect Cleanse is based on this idea.
- Evidence: Researchers found that serum from calorie-restricted animals was able to delay senescence of normal human fibroblasts in vitro and significantly increase their lifespan in these cells, when compared to serum from ad libitum fed animals. (Study link) A 2021 human trial with 100 volunteers showed that 3 cycles of FMD reduced inflammation and improved metabolic markers, hinting at anti-senescence effects. Using a FMD in combination with cancer treatments has been shown to boost the responsiveness and effectiveness of the therapy. Women using the FMD had about a 4-fold higher chance of a response to the neoadjuvant chemotherapy compared to the control group. (Study link)
- Try it: Periodic FMD (5 days every 1–3 months) is a great choice, and much more powerful than intermittent fasting. Still time-limited eating is a good idea, but not very powerful as a fasting method.
Putting It All Together
When you combine a plant-based diet that has all of these great phytochemicals in it along with some hormetic stress inducing lifestyle practices, you get a recipe for healthy aging and a long healthspan. You might be doing some of these practices already. Sauna? Yes, good choice. Cold plunge? (Like I said, you first, but I prefer the sauna, as heat feels so good.) Of course, exercise is great. How about adding in a seasonal Perfect Cleanse to your routine twice a year? That is an excellent evidence-backed choice.
