Preview: Here’s a sneak peek at what we’ll be talking about in today’s newsletter:
- What zombie cells are and why we want to get rid of them.
- How a regular cell can turn into a zombie cell.
- Top tips on how to kill your zombie cells.
Your body comes programmed with a natural intelligence that’s designed to maintain balance and keep things running smoothly. One way it does this is by cleaning up damaged cells that are a byproduct of normal, everyday metabolism. As we age, our cell’s built-in quality control takes a hit (more on this below), and damaged cells aren’t able to be cleared away as effectively anymore.
When damaged cells stick around, neighboring cells take a hit, too, making us more susceptible to diseases down the line. Today, I want to talk to you about what happens to our cell’s quality control as we age and how to activate your cell’s natural cleaning programs to lower your risk of age-related diseases.
Cellular Damage Control
When a cell is damaged and unable to sustain its function anymore, a process called autophagy (auto= self; phagein= to eat) is activated. Autophagy is our cells’ way of housekeeping—it sweeps up debris and repairs any damage done to the cell that keeps it from doing its job (1).
When the damage is beyond repair, apoptosis (or programmed cell death), is activated. This is a very normal process that occurs throughout our entire lives, from conception until the day we die. During development, the formation of a baby’s organs, fingers, and toes depends on apoptosis.
After birth and as we get older, apoptosis takes on a different role, getting rid of damaged cells to prevent them from replicating and forming a tumor. Apoptosis is advantageous because it only gets rid of damaged cells and preserves neighboring ones that are still working (2).
This means autophagy saves damaged cells that have the potential to be repaired and apoptosis destroys damaged cells that cost too much to fix.
Exposure to the Elements of Life
As we get older, our bodies are exposed to more stressors. Whether it’s processed foods, sugar, nutrient deficiencies, a sedentary lifestyle, stress, chemical toxins, or EMFs—these all cause inflammation that damages our DNA and shortens our telomeres, resulting in chronic disease and advanced aging, a phenomenon we call “inflammaging.”
As a result of inflammaging, our cell’s maintenance programs start to slow down. Instead of cleaning up or destroying a damaged cell, it becomes senescent, which means it can no longer replicate or perform its functions anymore (3). A senescent cell isn’t alive, but it’s not dead either—they sit in our organs secreting inflammatory cytokines that attract immune cells and damage nearby cells (3)(4)(5).
What is a Zombie Cell?
This half-alive, half-dead state is where we get the term “zombie cell” (6). Zombie cells refuse to die on their own and wind up damaging nearby cells, turning them into zombies, too.
The immune system can handle clearing zombie cells here and there, but once they start to accumulate, the damage and inflammation become greater and greater. Eventually, the immune system has a hard time keeping up.
Zombie cells tend to accumulate in certain areas like the joints, arteries, eyes, liver, and brain, which is why they’re found in osteoarthritis (7), cardiovascular disease (8), cataracts (9), fatty liver (10), and neurodegenerative disorders (11)(12). Even though they can’t divide, zombie cells increase the risk of cancer by secreting pro-inflammatory cytokines that damage nearby tissue (3)(13).
How to Kill Your Zombie Cells
Researchers in the senescence space are looking for ways to kill zombie cells. Senolytics, a class of drugs being researched for treating age-related diseases, target pathways that turn a cell senescent. Because the route a cell takes to turn senescent depends on many factors, this has proven to be pretty challenging.
Some drugs already exist that target age-related genes, like metformin. It’s not clear how metformin kills zombie cells in addition to being an antidiabetic drug, but drugs are repurposed all the time. Many researchers are cautiously optimistic about metformin because it could play a big role in addressing cellular senescence. I don’t personally take it, but I know some biohackers who do. Here’s a balanced write-up of the pros and cons.
Luckily, there are natural senolytics anyone can try to target these same pathways. One way to do this is hormesis.
What’s hormesis? If you’ve ever heard the phrase, “What doesn’t kill you makes you stronger”—that’s hormesis. It’s when your body is exposed to a mild stressor, and in response to that stressor, you come out stronger and more resilient.
In today’s protocol, I have some easy, safe, and effective evidence-based therapies you can try to activate hormesis and kill off your zombie cells. They’ll help lower your risk of chronic diseases associated with aging in order to extend your lifespan and healthspan.
I. Polyphenols. Polyphenols are plants’ built-in defense systems that prevent predators from eating them. This intelligent system triggers a reaction that causes enough harm to turn a creature away—bitter-tasting plants are one example. Some polyphenols are more dangerous than others and can cause severe illness, even death in animals and humans.
For the most part, polyphenols promote health by flipping on genes that upregulate antioxidant production, reduce inflammation, kill zombie cells, and slow the aging process (14). This is why plants have been used as medicine for thousands of years.
My friend and business partner Dr. Mark Hyman refers to this as “symbiotic phytoadaptation,” which basically means humans and plants live in harmony together. However, it’s worth mentioning that certain plant polyphenols have the potential to cause damage in susceptible individuals, like those dealing with gut issues or autoimmunity.
There are many different ways to activate hormesis (which we’ll get into), but in this section, I want to talk about some of the most widely studied polyphenols that promote healthy aging.
1. Resveratrol. This polyphenol has gained a lot of attention for its anti-aging, anti-cancer, and heart-healthy benefits (15), it’s found in red wine (don’t get too excited yet) and grape skin in trace amounts.
Resveratrol flips on a gene called SIRT1 that lowers inflammation and prevents cells from turning into zombies. It also turns off the mTOR (mammalian target of rapamycin) pathway, a requirement for autophagy. For more on the role of mTOR, see the section on fasting below. The SIRT1 gene and mTOR pathway both play huge roles in healthy aging (16)(17).
Most therapeutic doses of resveratrol have been tested in animal models, but are quite high when extrapolated over to humans. Based on the research that’s out there, and this conversation between Dr. Rhonda Patrick and Harvard professor/aging expert Dr. David Sinclair, a therapeutic dose seems to be anywhere between 250 and 1,000 mg per day (18), but the amount of wine that needs to be consumed to reach that dose is ridiculously high and winds up causing us more harm than good from the alcohol that’s there.
Most red wines contain anywhere from 0 to 2 mg of resveratrol per liter (19). On average, Pinot Noir seems to have the most resveratrol per ounce but it’s still not much at all (19).
There can be social reasons to enjoy a limited amount of wine (more on that in a future newsletter), but when it comes to resveratrol, you’re way better off getting your dosage from a high-quality supplement.
2. Curcumin. The active ingredient in turmeric, curcumin, has powerful anti-inflammatory effects primarily through its impact on the gut microbiome. Because it’s not very bioavailable, curcumin goes straight to the gut where it promotes the growth of beneficial bacteria strains, improves intestinal barrier function, and counteracts the expression of pro-inflammatory cytokines (20). These properties give curcumin its medicinal power that’s been used to treat a range of chronic diseases, including cardiovascular disease, cancer, and metabolic syndrome (21)(22).
Curcumin also increases the production of brain-derived neurotrophic factor, a protein that stimulates the growth of new neurons. Granted, this has been shown in animals, but it’s still pretty awesome. Any natural way to potentially preserve my brain mass and reduce my risk of diseases like Alzheimer’s—I’m all in (23)(24).
3. Quercetin. The most popularly consumed polyphenol in people’s diet, quercetin is found in capers, peppers, onion, and apples. When quercetin reaches the gut it is broken down and metabolized by bacteria, which are responsible for its anti-cancer, anti-inflammatory, anti-obesity, anti-diabetic, and anti-atherogenic effects. It also improves gut barrier function, protects the liver, and reduces fat oxidation (20).
4. Catechins. One of the main polyphenols in green tea, catechins are also present in cacao, apples, berries, grapes, and many other foods and herbs. When catechins reach the gut, they are broken down into metabolites. Green tea seems to be one of the easiest ways to get your catechins because of the quantity per serving.
Epigallocatechin-3-gallate (EGCG for short) is the most abundant and biologically active catechin present in green tea (20). EGCG feeds the good gut microbes, inhibits the growth of bad gut microbes, increases short-chain fatty acid production, and has anti-obesity and anti-cancer properties (20).
II. Fasting. Fasting is another hormetic stressor that turns off mTOR (25). When energy is abundant, mTOR is activated and stimulates growth (26). High insulin, sugar, or protein turn on mTOR which is good if you’re trying to build muscle, but not if it’s on all the time.
If mTOR is always active, autophagy can’t happen. And when cell clean-up isn’t going on, mTOR is active and encouraging growth, so the risk for cancer goes up. That’s why fasting is such a beneficial practice for aging because it turns off mTOR and turns on autophagy to get rid of zombie cells. Dr. Ben Bickman talks about this a bit more in this clipon Instagram.
Fasting also activates SIRT1 and PGC-1ɑ, a protein that stimulates mitochondria production and enhances energy metabolism (27). Fasting also programs your circadian rhythm for better sleep—a non-negotiable for healthy aging.
There are many metabolic benefits to fasting, but it’s not for everybody all the time. I wrote about this in a past newsletter. Women in their reproductive years might want to consider time-restricted eating instead of extended intermittent fasting to avoid causing stress that could interfere with their menstrual cycle. Check out this clip for a more detailed conversation I had with Dave Asprey about this topic.
Fasting can be a beneficial practice for many and there are a few different types. Based on your current health status and fasting experiences, it’s important to find what works best for you.
- Intermittent fasting. Intermittent fasting offers a ton of health benefits, but it can look different depending on who you ask. People typically go by periodic (14-16 hours without food) or prolonged (24-48 hours without food). Either way, feeding periods don’t make up for the calories lost during fasting, meaning your overall daily caloric intake is decreased.
- Time-restricted eating. Time-restricted eating is a safe alternative to intermittent fasting that has the same benefits. It doesn’t require calorie restriction but instead focuses on limiting eating to an 8-12-hour window during the day. Overall daily caloric intake stays the same. If you are new to fasting, this is often where people start.
- Fasting-mimicking diet. A 5-day period of intentional calorie restriction for one week out of the month. This fasting protocol was designed by Dr. Valter Longo as an adjunct to chemotherapy under a doctor’s supervision. It works by tricking your body into thinking it’s fasting and turns on the beneficial pathways mentioned above.This is why so many functional medicine doctors incorporate some element of fasting, into a larger protocol, for anyone battling cancer. The studies are ongoing, but Dr. Valer Longo has a great summary page here. Lastly, you don’t have to have cancer to benefit from the fasting-mimicking diet.
- 5:2 plan. A fasting regimen that includes eating a standard diet for 5 consecutive days followed by restricting calorie intake by 500-600 calories per day for 2 days (27).
- Eat-stop diet. Consists of 24-hour fasting once or twice a week and eating normally on the days you aren’t fasting.
Confused about fasting? My favorite free app on fasting education is called Zero and it was designed by Dr. Peter Attia to help people find the right fasting approach that works for them and track their fasting progress.
III. Physical movement. Exercise is another type of senolytic that lowers markers of inflammation and cellular aging (28)(29). Resistance training and cardio both offer unique benefits.
Resistance exercise causes slight tears in the muscle tissue that’s worked, which is why you might feel sore the day after. Heavily working muscle groups causes muscle breakdown and inflammation. In response, immune cells migrate to the site where repair is needed.
Having protein after resistance exercise helps speed up the repair process and promotes muscle growth (30) by turning on mTOR. But if you’re eating too much, your muscles eventually become mTOR resistant which mitigates muscle growth. That’s why incorporating a fasting regime with your workout is important because it turns off mTOR and gives your muscles the chance to repair, clear away zombie cells, and become mTOR sensitive again. Shout out to Dr. Ben Bickman who helped with my understanding in this area.
It seems like cyclical mTOR activation (not turned on or off all the time) provides the most benefit for healthy aging. Devoting 20-30 minutes 2-3 days a week to resistance exercise is really important for maintaining lean muscle mass, strengthening bones, and reducing your risk of sarcopenia (muscle loss), osteopenia (bone loss), and osteoporosis (weakened bones).
Aerobic exercise is also important for healthy aging. In addition to enhancing insulin sensitivity, maintaining a healthy weight, optimizing immunity, lowering inflammation, and keeping our lungs and heart strong, aerobic exercise also increases heart rate variability (HRV). Research shows HRV is a predictive biomarker of healthy aging because it means we can adapt better to stressful situations (31).
Increased HRV means a higher vagal tone—that’s your body’s ability to relax after a stressful situation. Having a high HRV emphasizes the parasympathetic nervous system (rest and digest) after a stressful event instead of the sympathetic nervous system (fight or flight). This means less cortisol, less inflammatory cytokines, less DNA damage, and fewer zombie cells (32).
1. Move throughout the day. We weren’t meant to sit for long periods of time without movement. Especially today where more of us are working from home, it’s important to get up and move throughout the day. Whether it’s a brief 10-minute walk, light stretching, or squats, breaking up your day with movement is a great way to get some exercise in. Plus, it helps you focus better when you go back to work. My rule of thumb is to make sure I move for at least 5 minutes at least every 90 minutes. What do I do? A quick set of squats, push-ups, or even a quick walk outside.
2. Target heart rate during exercise. A good goal for how high you want your heart rate to be during exercise is to aim for 180 minus your age (in years). For a 40-year-old, that would be 180 – 40 = 140 target heart rate. If you have diabetes, you might want to subtract 5 from that number. If you don’t have a device to track your heart rate, count your pulse for 15 seconds and multiply that by 4 for your heart rate.
Anything above your target heart rate is crossing into high-intensity interval training (HIIT) which is good to do a few times a week but any more than that can cause inflammation, damage, and stress on the body.
3. Move in a way that you enjoy. According to Dr. Valter Longo’s book The Longevity Diet, walking fast for an hour every day is a great way to promote optimal health, and it doesn’t have to be all at once. Walking for 20 minutes three times a day, to the library, a local coffee shop, or walking your dog is an awesome way to get it in (33).
What’s most important is picking an activity that brings you happiness, it doesn’t have to be something lame or dreadful you don’t enjoy. Choose something you look forward to, that’ll make it much easier and more enjoyable. If you are looking for more resources on finding the right movement for you, listen to this interview I did with Dr. Kelly McGonigal.
III. Sauna. The sauna is another great way to promote healthy aging by turning on genes that repair damage and lower inflammation. As another type of hormetic stressor, sitting in a sauna for at least 20 minutes at a temperature of 175°F can have some pretty incredible benefits (34).
For one, the sauna turns on genes that make heat shock proteins that repair and remove dysfunctional proteins and prevent them from clumping together—a risk factor for developing Alzheimer’s and Parkinson’s disease (35)(36).
What’s more, the sauna also activates genes that increase antioxidant production, repair damaged DNA, kill zombie cells, and encourages stressed cells to become more resilient. I know not everyone has access to a sauna, but there are ways to get the benefits without one.
1. Take a hot bath. If you have a bathtub, fill it up with hot water and submerge your entire body (chest cavity included) underneath. This is a great way to break a sweat and adding some Epsom salts can provide a little extra relaxation.
IV. Cold plunge. Periodically exposing yourself to cold temperatures turns on genes that help lower inflammation and reduce swelling. That’s why a lot of professional athletes take ice baths, to speed up their recovery. It’s also been linked to better immune function (37) and there’s evidence that it could be useful for treating depression (38).
Cold exposure also increases the expression of PGC-1ɑ, a gene that converts white adipose tissue to brown adipose tissue. This good fat tissue is more thermally active so it burns more calories, it’s also linked to a longer lifespan and health span (39)(40).
1. Take a cold shower. In traditional Chinese medicine, cold showers are said to get your chi (energy) flowing. Start off by taking a warm or hot shower at a temperature you feel comfortable with. Then, once your body warms up, turn the faucet to cold (enough where you start to feel uncomfortable). Stay underneath the water for as long as you can and focus on breathing deeply.
The next time you try it, make the water slightly colder and stay in for a minute or two longer than the last time. After doing this practice more you’ll start to get used to the colder temperature and might even enjoy it.
Wim Hof has a 3-part mini-class that’s free and includes a lesson from the “Iceman” himself on the power of breathing, cold showers, and your mind. It’s only 25-minutes long—I highly recommend it!
1. ResveraCell – Recently I’ve been taking this formula from Thorne which not only includes resveratrol, but also contains quercetin and nicotinamide riboside, a precursor of NAD+ (a molecule that gets a lot of attention for slowing the aging process).
A liter of red wine includes about 1.7 mg to 1.9 mg of resveratrol (19), this formula by Thorne includes 150 mg of resveratrol in addition to all the other good stuff mentioned above.
2. Ōura ring. I love wearable technology that gives me real-time feedback so I can know what’s going on with my health and adjust accordingly to get it dialed in. Ōura ring tracks your daytime and nighttime activity, which means it tracks your sleep (and I’m all about any way to optimize my sleep). Not only does it track your sleep, it also tracks your heart rate variability during sleep. As I mentioned earlier, HRV is a super important and predictive biomarker of healthy aging.
3. Sauna blanket. Saunas are expensive, but they are a straight-up game-changer. Sauna blankets can reduce inflammation, stress, and improve detoxification, all important for healthy aging. HigherDOSE (disclaimer: they are a podcast sponsor) Infrared Sauna blanket is an affordable and compact way to get all of the anti-aging benefits of sauna use without breaking the bank.
Because HigherDOSE is a podcast sponsor, they are offering the Try This Community $75 off an Infrared Sauna Blanket using my promo code DHRU75 at checkout.
No matter how hard we try to fight it, aging is a part of life that naturally happens to all of us. It’s not a question of when, but how can we feel our best along the journey? Maybe you’re already feeling the effects of getting older—that’s okay! I know I do too sometimes.
But the aging process doesn’t have to be all bad. If you’re moving every day, managing your stress levels, and eating a whole foods diet filled with quality protein, healthy fats, and plenty of polyphenols from fruits and vegetables, chances are, you’re in pretty good shape!
On top of those fundamental pillars of health, killing your zombie cells using the hormetic stressors listed above can help lower your risk for age-related chronic diseases and preserve your mobility and your mind for longer to be able to keep doing the things you love. Try incorporating some of my steps above into your daily life, starting with where you’re at today.
What do you know you can do first? Maybe that’s taking a supplement, a cold shower, or moving around in a way that feels good—these are all things you can start doing today to slow (or maybe even reverse) the aging process. That sounds like a pretty awesome pay-off to me.
Remember, it’s never too late to get started. Try my How To Kill Your Zombie Cells Protocol and let me know what you think with the feedback feature below.
Just a heads up! We’re absolutely loving hearing your feedback on the Try This newsletter! Starting next week, we’re going to be dishing out some more condensed protocols and would love to know what you think.
Be sure to look out for next week’s protocol Try This: What To Do About The Plastics We Can’t Avoid.
Here’s to your health,