Hello everyone! Welcome back to another Friday blog. Today I wanted to talk about Zombie cells. Most of us are familiar with The Walking Dead series and have a mental image of what a zombie looks like - and does…or doesn’t do. Zombies wander aimlessly about causing damage and taking up space. They aren’t dead…but not really alive either - they are “cells that are stopped from dividing but that refuse the body’s order to die, and instead exude an array of protein signals that change the tissue around them.” Zombie cells are implicated in many disease processes - such as cancer, dementias, metabolic disease, muscle wasting, osteoporosis and even early death - and can rapidly age you.

Zombie cells accumulate with age due to poor immune system clearance, mitochondrial dysfunction, and exposure to cell-damaging inflammatory agents - such as chemo, radiation, or environmental toxins. These senescent cells have a low pH due to high lysosomal content and leaky membranes - and are highly acidic. In order to survive, they produce an enzyme to help neutralize and increase pH. Researchers show that inhibiting this enzyme exposes zombie cells to unsurvivable internal acidity, leading to cell death. Their leaky membranes excrete inflammatory poisons and cytokines that cause wide-spread inflammation and damage to surrounding tissues - turning neighboring cells into zombie cells - aging us rapidly. You can think of a rotten apple in the barrel causing all those around it to rot too. So, what if you could not only kill these zombie cells, but rejuvenate or reverse the age of zombie cells so they behave like brand new stem cells? You could biologically age in reverse. WHAT??!!! Let’s delve in.

First, how do normal cells change and become zombie cells? “When a healthy human cell divides to create two identical cells, a little bit of DNA is shaved off the tip of each chromosome, causing telomeres to get shorter with each division.” Telomeres are the protective end-caps of our DNA. You can think of them like aglets (plastic end caps) on shoe laces - made up of mostly the same material -that prevent the ends from fraying. Telomeres protect our DNA in much the same way. “In humans, progressive telomere shortening is thought to be one of the mechanisms underlying organism aging.” Telomeres are “exquisitely sensitive” to oxidative stress. As one can imagine, damage to telomeres disrupts DNA replication and induces stress-signaling pathways that lead to senescence. Alcohol, smoking, poor diet, environmental toxins, sunlight and other factors generate massive ROS (reactive oxygen species) that damage DNA. Okay - so, unmitigated oxidative stress is at the root of the transition from healthy cells into zombie cells. This oxidative stress damages mitochondria - driving the production of more ROS. The accumulation of these cells drives up inflammation - creating more zombies and more damage.

How does the body remove or clear zombie, dead or damaged cells? This can only happen during autophagy (self-devour). Autophagy is a process that is turned on during fasting - normally, when we sleep (but there are other ways as well). This is when your clean-up crew goes to work. The body goes into a rest, healing and repair state. Your body is amazing at clearing out debris, taking apart dead, old or misfolded proteins, destroying old malfunctioning mitochondria - making new fully functioning ones - even producing pluripotent (can become any cell-type) stem cells that can become anything the body needs. Your body is so smart. This is also when your body gets rid of visceral fat, excess insulin (crinophagy - form of autophagy), apoptosis (programmed cell-death), and anything else it needs to clear out, remove, repair or rebuild in order to optimally function.

Autophagy really doesn’t kick in until about 18 hours. The longer you go, the more benefit you get - generally up to 72 hours. Longer fasts can be very beneficial in fighting cancer as well, but will require more preparation and coaching. Most of us are eating too frequently throughout the day and continuing to munch until we go to bed at night. Then, we eat first thing when we wake up! Our body never gets to stop working on digesting food. This is terribly exhausting to the pancreas as well as the liver. Constant eating not only continually spikes insulin over and over, but interferes with autophagy and sleep. We need to completely stop eating 3 hours before bed. So, implementing strategies to turn on autophagy helps to clear zombie cells from our bodies - but what about turning them into new stem cells that can be used anywhere?

Is there a way to reverse-age our senescent or zombie cells - turning them into fully rejuvenated cells? As it turns out, YES!!! In 2012 Yamanaka won the Nobel Prize in Physiology or Medicine for his discovery of 4 factors that can rejuvenate senescent cells into induced pluripotent stem cells. Researchers demonstrated “cellular senescence is not a limit to reprogramming and that age-related cellular physiology is reversible.” They showed these rejuvenated cells to have reset telomere size, gene expression profiles, mitochondrial metabolism and oxidative stress that is “indistinguishable” from human embryonic stem cells that are able to re-differentiate into fully rejuvenated cells. WHAT???!!! This is incredible! In mice receiving Yamanaka factors, researchers not only extended life by 25%, but also demonstrated accelerated muscle regeneration - no blood cell alterations - no neurological changes - and zero cancer. This is AMAZING!!!

So, HOW is this possible - and HOW much younger could we biologically become if we could turn these zombie cells into pluripotent stem cells that are in an “embryonic state?” Researchers and functional medicine doctors are anticipating we can live as long as 180 years or more.😳 This is where epigenetics (epi=above) comes in. “Epigenetics is dynamic and heritable modifications to the genome that occur independently of DNA sequence. It requires interactions cohesively with various enzymes and other molecular components. Aberrant epigenetic alterations can lead to inappropriate onset of genetic expressions and promote tumorigenesis. As the epigenetic modifiers are susceptible to extrinsic factors and reversible, they are becoming promising targets in multiple cancer therapies.” 

Epigenetic factors function to determine which genes are turned on, and which are turned off. You can think of your DNA like keys on a piano. It may be a very nice piano, but no note is played until someone strikes a key. Epigenetics determines what keys are played and what song is generated. If you are eating a diet rich in antioxidants and polyphenols (HP-EVOO), beautiful songs hitting all the sweet notes are played. If you are lacking these protective molecules (senolytics) - oxidative damage occurs and the wrong keys get played. This is how cancer genes get turned on - or off. We also now realize that these are heritable factors as well. Glyphosate, for example, causes modifications in DNA expression that lead to mammary tumors as well as infertility in particularly 3rd and 4th generation mice. So, what are the cellular hallmarks of aging that affect ALL of us and shorten our lives?

• Genomic instability – DNA damage that mutates cells and can potentially cause cancer and other harmful cell behaviours.
• Telomere attrition – The protective caps on our chromosomes erode which leads to loss of tissue regeneration.
• Epigenetic alterations – Changes to gene expression that makes cells old and more dysfunctional.
• Loss of proteostasis – Loss of efficient protein creation and the accumulation of cellular waste.
• Deregulated nutrient sensing – Failure of appropriate response to nutrients, cell growth, loss of energy production, and other cellular functions.
• Mitochondrial dysfunction – Free radicals and oxidative stress damage to the mitochondria leading to mitochondrial mutations and failure of energy production.
• Cellular senescence – Worn out damaged cells accumulates which lead to chronic inflammation and loss of tissue regeneration.
• Stem cell exhaustion – A loss in the ability of our stem cells to regenerate damaged tissues due to running out of healthy replacement cells.
• Altered intercellular communication – Altered cell-to-cell communication leading to chronic inflammation and dysfunctional cell behavior.

“Clearance of the cells in mice has been shown to delay or alleviate everything from frailty to cardiovascular dysfunction to osteoporosis to, most recently, neurological disorders.” Let’s look at some strategies to clear our bodies of zombie cells.

• Autophagy (self-devour) - “the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. It allows the orderly degradation and recycling of cellular components.” This involves calorie restriction or fasting, intermittent fasting or fast-mimicking - Giving your body a window of time away from eating to activate autophagy. You begin to see the initial phase starting at about 12 hours by increasing growth hormone - until autophagy kicks in ~ 18-24 hrs for most of us. Some people can take up to 4 days. The longer you go, the better the clean-up. At roughly 72 hours your production of stem cells kicks in. Several super-foods also stimulate autophagy, such as HP-EVOO! If you are battling cancer, try fasting x 23 hours/day and consume HP-EVOO, cruciferous vegetables and very clean protein - combined with an extended fast of 48-72 hours. This will go a long way in activating your body’s autophagy systems to destroy the cancer and eliminate cancer’s food source - sugar/glucose. Always consult your physician before implementing.
• Senolytics are molecules that destroy or ‘lyse’ senescent cells. Eating foods that contain these “super-powers” can eliminate zombie cells and reverse biological age. Some of these include oleuropein, tyrosol, hydroxytryrosol - EVOO,  quercetin - capers, onions and apples, curcumin - turmeric - use whole root or ground, capsaisin - peppers, fisetin - strawberries, cucumber, onions and apples and adaptogenic mushrooms - such as lion’s mane, shiitake, cordyceps, turkeytail, reishi and chaga to name a few. They are developing senolytic drugs as well. Metformin is one that works by lowering insulin - but there are side effects with drugs.
• Uncouple mitochondria - ketones (MCT oil, sheep and goat milk and cheeses) and polyphenols - (HP-EVOO, colorful veggies and fruits) are powerful mitochondrial uncouplers. This speeds metabolism by increasing mitochondrial population and preventing damage. This increases your power force - while simultaneously throwing away 30% of calories in the form of heat. This is 30% more calories that you can consume without actually using or storing it as fuel.
• Cold exposure - hormetic effect - short-term physical stress that produces a healing response in the body. Cold exposure stimulates mitochondrial uncoupling, enhanced blood flow following exposure and stimulation of anti-inflammatory pathways in the body. Take a hot shower or sauna followed by ice cold shower or cold plunge into your tub. This activates a spectrum of healing pathways in the body and stimulates mitochondrial uncoupling and production of new and upgraded mitochondria.
• Microbiome - fix your gut. Pathogenic microbes interfere with autophagy processes. When the pathogenic microbes out-number the beneficial ones, you get widespread inflammation. HP-EVOO heals the gut lining, feeds our beneficial gut microbes who LOVE polyphenols and ketones and selectively kills pathogenic microbes. Eating fermented foods supplies natural probiotics - sauerkraut, kimchi, miso, natto help restore balance in the gut. Beneficial microbes produce nitric oxide, B vitamins, butyrate and other short-chain fatty acids that activate healing anti-inflammatory pathways in the body. Check out blog # 46! 
• Methyl donors - Eating foods high in choline, betaine and sufurophane supply “methyl donors” that epigenetically modify expression of DNA. “Some of the epigenetic mechanisms that modify gene expression without modifying the genetic code depend on the methylation of DNA or of histones; and diet availability of choline and other methyl-group donors influences both of these methylations.” When choline metabolism is disrupted in mice, they develop liver cancer. Consume dark green leafy vegetables, beets, spinach, cruciferous vegetables, pastured eggs, fish and liver.
• HDL-C (cholesterol) - >90 is associated with epigenetic lower aging rate. The “sweet spot” with the BEST PROTECTION from CVD (cardiovascular disease) for women = 92.8mg/dL; men = 73.5mg/dL. “Studies have shown that high HDL-C levels have protective effects on atherosclerosis and CVD across multiple populations.” Individuals with high HDL-C have a lower risk of death compared to lower HDL-C levels, independent of CVD diagnosis. They also show that high triglycerides are a more predictive factor for CVD.
• Waist circumference - Researchers looked at 650,000 adults and found a strong association between increased BMI - Class I obesity (30.0-34.9)  (overweight) 25.0-29.9 - increased waist:hip ratio - ideal: women <.8 - men <.9 -  waist circumference - men 33.5-40” women 25.5-34” - and accelerated epigenetic longevity clocks. Men with a waist of 43” had 50% increased risk of death than men with 37”. Women with 37” waist had 80% higher risk of death than women with 27.5”. EVOO helps with weight-loss.
• NAD⁺ - Nicotinamide adenine dinucleotide (NAD⁺) -  is a coenzyme for redox reactions - central to metabolism and mitochondrial function. It is derived primarily from forms of B3 or tryptophan. Unfortunately, the levels drop by 50% every 20 years. So, by the time you are 20, levels are 50%. When you are 40, you are down to roughly 25%. By the time you hit 60-70, you are very low. NAD+ gets used up fast with inflammatory molecules such as CD38, which doesn’t leave enough for our longevity and health promoting team of sirtuins. “Nicotinamide can directly and indirectly influence many key cellular functions, including metabolic pathways, DNA repair, chromatin remodelling, cellular senescence and immune cell function.” Increase these levels through HP-EVOO, Apinegin (high in dried parsley), rutin, B3, exercise, fasting, hot saunas, limiting UV exposure (use it up fast).
• Exercise - Enhances blood flow throughout the body, provides a hormetic effect by temporarily increasing ROS (reactive oxygen species) and stimulating your body’s anti-inflammatory pathways, improving immune function while eradicating pathogens, increasing mitochondrial number and function and NAD+ production. Check out blog # 65!
• Eliminate sugar and fructose - they MAKE ZOMBIES - cut out liquid sugar - alcohol, beer, soda, sweetened coffees and teas. They drive up glucose and insulin, causing widespread damage.
• Lower fasting Insulin - Choose to stop spiking insulin. Increase dietary fiber - most carbohydrates should come from vegetables and fruits - stop eating frequently and eliminate sugar bombs! Ask your MD to include fasting insulin to your bloodwork. Increase your good fat intake. HP-EVOO, MCTs, avocados, grass-fed Ghee and omega 3s are amazing at helping to get this number low. Boston Heart’s newest recommendation is fasting insulin of <3. On bloodwork, you’ll see a range from ~ 2-22. The ideal range is 1-3. They noted several markers for increased all-cause mortality above 3.
• Eat organic - By choosing organic, you avoid glyphosate (mostly - it’s in rain now) and avoid artificial preservatives, colors and flavorings, since it’s not allowed in organic foods.
• Eliminate processed foods they are poison to your mitochondria and your microbiome. They are obesogens - directly cause fat deposition and obesity. For example ~2,000 synthetic chemicals can be used in conventional packaged foods! Also, nearly 25% of conventional cereals contain BHT (butylated hydroxytoluene). The NIH report on carcinogens stated BHA is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.” In a study using rats fed a diet containing BHT, researchers noted lower litter numbers and birth weights in pups. It caused both benign and fore-stomach cancer in lab rats and hamsters, and liver cancer in fish.  It is included in the framework of The French National Strategy on Endocrine Disruptors since 2012.  Is also on the Danish carcinogen list. BHT and BHA (butyrate’s hydroxyanisole) are synthetic antioxidants - preservatives with widespread use in food, food packaging, animal feed, cosmetics, rubber and plastic products. FYI- both toluene and anisole are chemical solvents. I could only find one human study - Netherlands study in 2000 showed no association between stomach cancer and low-level “usual” intake. They only looked at them for ~ 6 weeks. Unfortunately there have been no human studies here in the US - These chemicals are everywhere and in everything - I, personally, am about to take a magnifying glass to my makeup and throw out whatever I find it in! Who in their right mind thinks this is okay to ingest and put on your skin?!!!!
• Guard Sleep - studies have shown a correlation between decreased REM sleep and autophagy dysfunction in clearing debris from the brain. “Autophagy dysfunction is associated with acute and chronic neurodegenerative and patho-physio-behavioral changes, which are also associated with REM sleep loss.” Researchers also noted elevated noradrenalin levels associated with REM sleep loss. Get bright sunlight first thing in the am. Turn down lights after dark - use infrared. Stay away from blue light - phone, computer screen, TV, LED lights…
• Micronutrients - Critical for building proteins and enzymatic reactions in the body. Zinc, for example, is bound to 10% of all human protein and is a cofactor in >300 enzymatic reactions. Selenium is structurally integrated into selenoproteins, magnesium is required for ATP to be biologically active in the body! - and is a cofactor in >600 reactions. Vitamin D is involved in innumerable processes and critical for thyroid and immune function. More than 50% of Americans are deficient in one or more. Our needs vary depending on how much sleep we’ve had, how much stress we are under - so it is dynamic in nature. The RDI is based on the minimum to prevent disease - not to optimize health.
• HP-EVOO - High polyphenol EVOO - As we learned earlier, HP-EVOO stimulates autophagy, is a natural senolytic, uncouples your mitochondria, feeds microbiome and heals leaky gut, helps raise HDL-C and lower triglycerides, enhances immune function for clearance from the body, prevents and reverses NAFLD (non-alcoholic fatty liver disease), cardiovascular disease, T2D (type 2 diabetes), Alzheimer’s (T3Diabetes), dementias and many other health issues. 

So, until next time my friends…Don’t turn into a ZOMBIE!! Drink, Drizzle, Digest HP-EVOO 2-4T raw daily, - use more for cooking and drizzling onto your food - eat the rainbow of organic or wild-sourced veggies (7-9 C) and low-glycemic fruits (to get the rainbow of gut microbes!) Eat wild-caught, pasture-raised, grass-fed, get plenty of sunshine + supplement magnesium, zinc, vitamin D3 + K2, get your trace minerals and electrolytes with good sea salt *Himalayan was formed before plastics, eat foods high in lutein, drink your body weight in oz of water, get a good pre/probiotic (if you have wiped out your gut microbes with antibiotics), consume indigestible fiber for your gut microbes, fermented foods for the post-biotics, adaptogens (such as mushrooms) and methylation donors (kale, beets, spinach, cruciferous, lion’s mane…), marjoram, rosemary, oregano, parsley and other herbs to detox, enhance overall health and reverse aging and disease, exercise your body and mind, add a few minutes of mindful meditation to your day to combat stress, take a hot epsom salt bath and follow with a cold shower/plunge, remove EMF (electromagnetic frequency) devices and blue light, use IR (infrared) from incandescent lighting, candles (check for toxic chemicals) or fire or in the evening to enhance sleep and...turn off the light!!   #HP-EVOO

Not intended to substitute medical care. Consult your physician.