Reverse Aging: Reanimating and Slaying Zombie Cells Naturally

Reverse Aging: Reanimating and Slaying Zombie Cells Naturally

by | Aug 28, 2023 | Brain Health, Healthy Aging, Herbal Medicine, Prevention

Time goes by so quickly, in a blink really! I felt this so much last week as my son, Vincent James, started his first day of second grade! We may feel like we are in a time warp, our cells don’t and as time marches on, our cells undergo a complex series of changes that lead to decreased functionality and increased vulnerability to diseases. One of the key players in this process is cellular senescence, a state in which cells lose their ability to divide and function properly, contributing to chronic inflammation, tissue dysfunction, and age-related diseases. Yes, time marches on and various stressors contribute to the aging process, however, one of the things that I get excited to see is the important role that lifestyle and natural medicine have in combating healing our bodies at a cellular level and helping to slow this aging-process, helping us to age well! Cellular senescence is one of the many topics I had the privilege  of learning more about this past spring at Medicines from the Earth in Ashville, North Carolina with the amazing naturopathic doctor and herbalist, Dr. Mary Bove. She shared some of the recent scientific research that have unveiled natural compounds, such as quercetin and fisetin, as powerful senotherapies capable of rejuvenating senescent cells and promoting healthier aging. She also discussed the so-called ‘hit-and-run’ dosing that seems to make these senolytics most effective. Hit and run dosing = less supplements to support well-aging. Interested to learn more, read on!

The Underlying Mechanisms of Cellular Senescence & Zombie Cells

Cellular senescence is a double-edged sword. While it serves as a protective mechanism against cancer by halting the growth of damaged cells, it also contributes to chronic inflammation and tissue deterioration. Senescent cells accumulate over time due to various factors including DNA damage, oxidative stress, and telomere shortening. These cells enter a state of persistent inflammation and release harmful molecules that can negatively impact neighboring cells and tissues, creating what is often referred to as the "senescence-associated secretory phenotype" (SASP). Because they are not yet dead, but not functional, and create havoc in the body, these senescent cells are also know as zombie cells.

Reanimating versus Slaying Zombies

SASP inhibitors (senomorphics) and senolytics are both approaches aimed at addressing aging-related cellular changes, but they work in different ways. Senomorphic agents morph the signals coming from the zombie cells, while senolytic agents directly target and eliminate these problematic aging cells. SASP inhibitors can be thought of agents that help to turn back zombie cells into healthy cells, like in science fiction zombies being reversed or reanimated back into healthy humans, whereas senolytic agents are the zombie slayers in this analogy. Another difference between SASP inhibitors and senolytics is related to how these agents are dosed. Daily dosing seems best for SASP inhibitors, while senolytic agents appear to work best with intermittent or ‘hit-and-run’ dosing.

Hit & Run Dosing

I know, know, zombie cells and ‘hit-and-run’ dosing, what is going on! While I didn’t come up with these terms, I cannot deny they are catchy and on-point. I was particularly excited to learn about how hit and run dosing seems to make these senolytic agents most effective. Hit and run dosing is exactly what it sounds like, using a higher dose of these agents for just a few days and repeating for at least several months in a row. I am always excited to learn about health supportive strategies that are relatively easy to implement and involve less pills!

Slaying the Zombie Cells with Lifestyle & Botanical Agents, Quercetin and Fisetin

Foundational lifestyle measures are pivotal for maintaining cellular health and combating cellular senescence. Regular exercise, a balanced diet, stress reduction, and other healthy practices play a crucial role. Intermittent fasting has garnered attention for its potential impact on cellular rejuvenation. By cycling between eating and fasting periods, intermittent fasting stimulates processes like autophagy, aiding in the removal of damaged cells. This approach shows promise in reducing the presence of senescent cells and supporting prolonged cellular vitality. Two natural compounds that have garnered significant attention as helping to improve cellular heath are quercetin and fisetin, through their actions as both SASP inhibitors and senolytics.

Quercetin

We’ve heard a ton about quercetin in recent years because of its immune supportive and anti-viral benefits. Quercetin is a plant compound called a flavonoid found abundantly in fruits and vegetables and some medicinal herbs (ie elderberry syrup and green tea), quercetin has been extensively studied for its antioxidant and anti-inflammatory properties. Recent research has highlighted its potential as a senolytic agent. By interfering with pathways that promote cell survival in senescent cells, quercetin helps induce apoptosis, or programmed cell death, in these cells. This remarkable action contributes to the removal of senescent cells from tissues, reducing inflammation and potentially delaying age-related diseases.

Fisetin

Another flavonoid and senolytic agent, found to help our bodies as well , not as well know by the general public is fisetin, found in foods like strawberries, apples, grapes, onions, cucumbers, and in higher amounts in the many trees such as various Morus species (Mulberry leaf), Cotinus coggygria (Smoke Tree) and Rhus succedanea fruit wax (the fruit of a sumac tree native to Japan). The fruit of North American species of sumac also contains fisetin, but have not been as well studied - yet. Fisetin, through its ability to modulate the senescence signaling pathways research suggests it can help our cellular ‘powerhouses’ or mitochondria function despite stress, combats aging in brain clean-up cells called microglia by increasing the production of the important antioxidant called glutathione and thus decreasing inflammation. All these actions work together to slow down age related changes in our aging bodies and brains!

The effects of quercetin and fisetin as senolytics are profound. Not only do these natural compounds aid in the elimination of senescent cells, but they also exhibit the potential to rejuvenate surrounding cells and tissues. As senescent cells are cleared away, inflammation decreases, and the tissue microenvironment becomes more conducive to healthy cellular function. What I find so exciting is that when dosed regularly in lower doses quercetin and fisetin can help to manage inflammation and cellular damage, but at when dosed intermittently and in higher doses the so called ‘hit-and-run’ dosing they act as senolytics, slaying the zombie cells that contribute to our aging.

Beyond Cellular Senescence

The implications of quercetin, fisetin and other botanical senolytics (ie gingerenone A from ginger and piperlongumine from black pepper) extend beyond their senolytic properties. Those of you who have worked with me for years, likely already know how much I appreciate natural therapeutics that are “multi-fers”, a term I’ve lovingly coined for natural agents that have multiple health promoting properties. I’ve long appreciated quercetin for being one of these agents. Both quercetin and fisetin have been studied for their potential in reducing the risk of chronic diseases such as cardiovascular disorders, neurodegenerative conditions, and cancer and research on botanically derived senotherapeutics is on the horizon. Their antioxidant and anti-inflammatory actions may contribute to overall wellness and longevity.

Conclusion

The discovery of natural senolytics such as quercetin and fisetin represents an important advancement in the field of aging research. By targeting and removing senescent cells, these compounds offer a unique opportunity to rejuvenate aging tissues and potentially delay the onset of age-related diseases and are with a relatively low side-effect profile compared to the pharmaceutically based senolytics. The potential for healthier aging through a well-aging lifestyle and the application of these natural therapeutics is good news for those of us who want to both optimize our health and age as well as we can.

 Dr. Sarah Giardenelli is a naturopathic doctor, acupuncturist, herbalist, owner of Collective Health Center. She is passionate about optimizing patients’ health, including strategies to age well. If you are interested in aging-well with lifestyle, natural medicine, and personalized supplements, including senotheropeutic and senolytic agents, please feel free to schedule or reach out to her office.

References

Bove, Mary. Sencescene, Senolytics, and Aging. Medicines from the Earth Herb Symposium Conference Proceeding Notes, 2023. https://www.botanicalmedicine.org/

Chaib S, Tchkonia T, Kirkland JL. Cellular senescence and senolytics: the path to the clinic. Nat Med. 2022 Aug;28(8):1556-1568. doi: 10.1038/s41591-022-01923-y. Epub 2022 Aug 11. PMID: 35953721; PMCID: PMC9599677.

Liu X, Wang Y, Zhang X, Gao Z, Zhang S, Shi P, Zhang X, Song L, Hendrickson H, Zhou D, Zheng G. Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation. Bioorg Med Chem. 2018 Aug 7;26(14):3925-3938. doi: 10.1016/j.bmc.2018.06.013. Epub 2018 Jun 18. PMID: 29925484; PMCID: PMC6087492.

Moaddel R, Rossi M, Rodriguez S, Munk R, Khadeer M, Abdelmohsen K, Gorospe M, Ferrucci L. Identification of gingerenone A as a novel senolytic compound. PLoS One. 2022 Mar 29;17(3):e0266135. doi: 10.1371/journal.pone.0266135. PMID: 35349590; PMCID: PMC8963586.

Rayne S, Mazza G. Biological activities of extracts from sumac (Rhus spp.): a review. Plant Foods Hum Nutr. 2007 Dec;62(4):165-75. doi: 10.1007/s11130-007-0058-4. Epub 2007 Oct 2. PMID: 17909971.

Tsurudome N, Minami Y, Kajiya K. Fisetin, a major component derived from mulberry (Morus australis Poir.) leaves, prevents vascular abnormal contraction. Biofactors. 2022 Jan;48(1):56-66. doi: 10.1002/biof.1798. Epub 2021 Oct 23. PMID: 34687255; PMCID: PMC9298084.

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5 Tips to Beat the Winter Blues

5 Tips to Beat the Winter Blues

by | Nov 17, 2022 | Brain Health, Mindfulness, Stress Management

While it's not yet officially winter, it's certainly starting to feel like it with the leaves off of the trees, frost on the ground, darkness, and cold to the bone weather upon us. Many have started to feel the impact of this change on their moods, which is known as seasonal affective disorder (SAD). Common symptoms include: depression, overeating, sleep changes, irritability, and self isolating. The sun lifts us up so much and sometimes we don't realize how much until we see her less! So in this newsletter I offer up a 5 tips (or reminders) on how to beat back these winter blues. 

1) Thanksgiving, an expression of gratitude, is a great elixir for the blues. I am daily thankful to be in alignment with my calling to support people on their health and healing journeys and grateful for you, my amazing patients and for the practice that I have been able to build with all of your support! When I am having a challenging day or drop into a pattern of "stinking thinking" I like to remind myself of three good things that happened that day that I am grateful to God for. The simple three good things practice is easy to implement and a surprisingly effective way to get back into a state of peaceful alignment.

2) Light! Specifically shining a 10,000 Lux white light box toward ones face, so the light is hitting the eyes from the side, for 10 to 30 minutes every morning is a wonderful, natural way to increase those mood boosting neurotransmitters, serotonin and dopamine. Some of my patients find using a sunrise alarm clock, which is a type of light that is connected to an alarm clock and stimulates the sunrise to help wake you up, also helpful.

3) Keep it Moving. With it being so dark out many of us literally might arrive to work when it's dark and then leave when it's dark. If you can carve out time for a walk, even a short 15 minute walk outside at mid-day has been shown to be as effective as light therapy for seasonal mood support. Aiming for regular cardiovascular exercise and strength training also has significant benefits for the mood and overall health. 

4) Build Community! Many people are suffering from loneliness, an epidemic that was only made worse during the pandemic. Faith communities, gym/ sporting groups, dance groups, coral groups, and Meet-up groups all can provide opportunities to build community. Volunteering can also be a great way to build meaningful connections - Loudoun Cares is a local non-profit organization that helps to connect Loudoun County residents to volunteer opportunities. Additionally, this article from Green America offers several other suggestions on how to build community - including time banks - which is an interesting, modernized version of the barter system, where members receive and exchange each others time and talents.

5) Have a Cup of Tea. My favorite mood boosting tea is tulsi or holy basil. But there are many others such as chamomile, lavender, and lemon balm that can help calm the nervous system and boost our moods. The ritual of having a cup of tea is calming in and of itself.

If your symptoms are so severe that they are impacting your ability to live a normal life, please seek out care from your primary care provider. I am here to help too. Naturopathic and East Asian Medicine - including herbal medicine and acupuncture - have so much to offer for support! Reach out to me on the form below to learn more about my healing practice.

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Alcohol, Immune Health and More: A Holiday PSA

Alcohol, Immune Health and More: A Holiday PSA

by | Nov 30, 2020 | Brain Health, Cardiovascular Health, Endocrine/Hormone Health, Immune Health, Mindfulness, Stress Management, Women's Health

The holiday season is a particularly stressful time for many people – and this year has been extra, as the kids say. One theme I often see in my patients is a tendency to use alcohol to relax. Most do not realize they are consuming a moderate or heavy amount of alcohol and many are not aware of the various health effects associated with each. Especially during this season and with alcohol sales soaring in Virginia, I feel compelled to provide a public service announcement. On September 3rd, the Washington Post wrote: “The Virginia Alcohol Beverage Control Authority brought in $1.2 billion in revenue during the 2020 fiscal year in a nearly $120 million increase from the previous year, even as the coronavirus pandemic left restaurants and bars shuttered for months.” As a health care provider, while not shocking, this is concerning, especially given the known, deleterious health effects of alcohol on the immune system.

When we talk about alcohol and its effect on the body positive or negative, we really need to consider the amount we are talking about. A standard alcohol drink is 14 grams of alcohol which equals 12 ounces of beer (~5% alcohol), 8.5 ounces of malt liquor (~9% alcohol), 5 ounces of wine (~12% alcohol), 3.5 ounces of fortified wine (ie sherry or port), or 1.5 ounces of liquor (distilled spirits, 40% alcohol). Moderate alcohol consumption for women is, as considered by the USDA, to be no more than one standard alcoholic drink per day and for men no more than two standard alcoholic drinks/day. Heavy alcohol consumption for women is considered, by the USDA more than 7 standard alcoholic drinks per week or more than 3 standard alcoholic drinks in one day and for men more than 14 standard alcoholic drinks per week or more than 4 standard alcoholic drinks in a day.

 

Light to moderate alcohol consumption has some likely effect in cardiovascular disease, where it has been shown to reduce risk of plaque build-up and heart attack and deaths from heart disease. One to two alcoholic drinks/day increases protective HDL and Apo A1 cholesterol, decreases LDL, triglycerides and ApoB (an inflammatory cholesterol fraction), decreases factors that influence blood clotting, may decrease systolic blood pressure, has been shown to reduces inflammatory marker blood biomarker, hsCRP. However, light to moderate consumption does not seem to have any effect in men with already established coronary heart disease. This is a major caveat to be aware of as many people in the US already have evidence of established heart disease and with the obesity epidemic we are seeing heart disease in children. About half of all Americans are at risk for heart disease and heart disease is the leading cause of death in the United States. 

Although red wine has been touted as ‘better’ than other forms of alcohol there is no conclusive evidence from clinical studies. Often people point to the polyphenol resveratrol that is in red wine as a reason to drink. However, you would have to consume a TON of red wine to get any benefit from the resveratrol in it. Most of the resveratrol in supplements is not from grapes, but from Japanese knotweed - an herb that grows like a weed in the US. Also, most of the research on the single ingredient resveratrol is insufficient. However, Japanese knotweed with all of its many phytochemicals is a wonderful herb that has been used in Traditional Chinese Medicine for centuries for its properties that have immune supportive effects and anti-inflammatory effects. 

Additionally, fruits and veggies generally have more polyphenols than wine. Most people would do better to focus on getting 5-10 servings of veggies and a few fruits per day and herbals teas and avoid drinking alcohol. One of my absolute favorite herbals teas of late is Holy Basil or Tulsi – as it has both a calming and gentle energy boosting or stress managing effects as an adaptogen herb.

I have a lot of patients with estrogen dominance, which is having too much estrogen in ratio to progesterone which contributes to many common PMS and other female health concerns. Alcohol only exacerbates these symptoms. Additionally, I have many patients at increased risk for breast cancer, sleep disturbances and symptomatic menopause. I generally advise limiting alcohol in these populations. 

While many people use alcohol to help relax before bed, the medical evidence shows alcohol to be disruptive to the sleep cycle. Magnesium chelates, Epson salt baths, meditation area some examples of more effective and less harmful choices to help get relaxed before bed or to get relaxed in general. Stress cannot be drunk away, as a culture the research shows that we all may benefit even when a small group of individuals takes some time daily to meditate. No time for meditation? Consider tapping or the Emotional Freedom Technique, which is a simple and often effective method for helping to relieve mild stress and worry. 

Known risks of over consumption or dependence include: central nervous system effects (kills your brain cells, as alcohol is a cellular toxin), cirrhosis (liver inflammation and damage), malnutrition, and mouth/esophageal/ laryngeal/liver cancer. More than two drinks per day can increase the risk of cardiovascular disease and overall mortality. Light to moderate consumption can increase risk of hemorrhagic stroke. In women, one or more alcoholic drinks per day might increase risk of breast cancer by 2 to 15% and increase mortality from breast cancer as much as 30% (especially if daily intake of folate is 300 mcg or less). Alcohol consumption can also increase asthma and migraines in those sensitive to sulfites/ yeast. 

I have many patients with acid reflux who are drinking 1-2 drinks every night, possibly along with caffeine, and often soda. While it is no surprise to me, they are often pleasantly surprised when their acid reflux resolves after eliminating these known triggers. 

Because alcohol increases your liver’s detoxification pathway alcohol consumption, it can disrupt the metabolism of many medications. Birth control is a good example of this, it is not as effective when drinking alcohol, so using a second method of birth control during these times is particularly important if trying to prevent pregnancy. There are many other medications affected by alcohol consumption and if you take medications you should be sure to check with your doctor or pharmacist to see if any can be consumed with alcohol. 

If you have pre-diabetes or diabetes, you might consider reducing your alcohol consumption. While light drinking can contribute to low blood glucose, heavy drinking can cause insulin resistance, which leads to the development of type II diabetes. Heavy drinking can cause inflammation of the pancreas and destroy the pancreas’ ability to make insulin, leading to diabetes. Alcohol is nutrient light and high caloric. “One pint of lager can be equivalent to a slice of pizza.” Over-consumption can contribute to weight gain and obesity, an independent risk factor for many diseases.

A final note during this season is that alcohol consumption weakens the body’s immune system making it more susceptible to disease and infection. Drinking more than 3-4 drinks on a single occasion will suppress the immune system even up to 24 hours later. Chronic drinkers have higher rates of diseases like pneumonia and tuberculosis.

For further reading on this topic, Harvard’s Nutrition Source has a thorough summary of the research on alcohol and its effect on the body: http://www.hsph.harvard.edu/nutritionsource/alcohol-full-story/

Dr. Sarah is passionate about educating patients and getting to the root cause of their chronic, troubling symptoms; often alcohol is often a culprit that has not been thoughtfully considered. Dr. Sarah is honored to be a collaborative partner in her patient’s health at her practice Collective Health Center, in downtown Leesburg, Virginia. As the saying goes, ‘it takes a village’ – particularly when sensitive issues, such as dependence are involved, the primary care provider, the behavioral health specialist, the naturopathic doctor and others may need to work together to help get patients back on the road to wellness.

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CBD: Making Your Own!

CBD: Making Your Own!

by | Mar 20, 2019 | Brain Health, Digestion/GI Health, Endocrine/Hormone Health, Herbal Medicine, Naturopathic Medicine, Stress Management

This is the first in a series of blogs I am going to present on the topic of cannabinoids and CBD. As it is the first day of spring, I figured it is the perfect day to start discussing America’s favorite weed, hemp. Since the 2018 Farm Bill has made it legal to grow hemp, there seems to be more and more interest and comfort using CBD and its relative marijuana medicinally. Indeed, I am seeing more and more folks using on their own, typically to manage issues with the mood or pain, without really understanding why or any concerns or contraindications they should be aware of.

A Few Cautions with CBD 

Family history of schizophrenia? Did you know that marijuana doubles the risk of psychosis in vulnerable individuals. Personal or family struggles with addiction? Did you know that marijuana is just as addictive as any other substances with addictive potential (caffeine, alcohol, cocaine, etc). About 9% of the population who uses will likely become dependent upon it. While CBD products, without the THC, do not seem to confer this addictive potential and can actually be useful in helping in cases of dependence – do you really need them? This last question is really one to address with your health care provider. However, did you know that you can make your own cannabinoids? I don’t mean in the kitchen – I mean in the body (although some of our favorite culinary spices can help our bodies make our own cannabinoids too!). There are more cautions that I will address in future blogs. Here I want to focus on how you can help your body make its own cannabinoids.

Make Your Own CBD! 

The cannabinoids that your own body makes are called the endocannabinoids and they help to regulate the cannabinoid system in our bodies that helps to regulate everything from mood, cognition, hormones, immune function, gastric motility, reproduction – including attaining and maintaining pregnancy, pain, pre and post and natal development - and we have the capacity to make our own! The endocannabinoids are fatty acids that are derived from arachidonic acid, which comes from consuming animal meats or from our body converting plant oils, such as from nuts, seeds, or cooking oils, into arachidonic acid. Too much arachidonic acid has been considered inflammatory. You might have heard about the importance of the balance between omega-3 and 6 fatty acids, it has been theorized that our America diet is generally low in omega-3 fatty acids that help to combat inflammation, and that a balance between is thought to help combat inflammation. Both omega-3 and 6 fatty acids are important for human health, but there are some people who struggle to convert omega-6 fatty acids into arachidonic acid. This is related to genetics and can be exacerbated by a vegan diet. These issues with impaired conversion, is part of the struggle with anxiety in some, not all folks, on a vegan diet, as there is not the building block available. 

The Endocannabinoids 

The arachidonic acids is converted into our endogenous endocannabinoids: anadamide, anandamide (N-arachidonoylethanolamide, AEA), 2-arachidonoylglycerol (2-AG), and palmitoylethanolamide. These serve as ligands or binding proteins to receptors, known as the cannabinoid receptors (CBD receptors), and their binding or complexing is what causes the changes in the body. 

Top 8 Ways to Make Your Own - CBD 

There are many ways we can both increase and decrease our body’s natural CBD that will be outlined in future blogs. Here I will focus on the top 8 ways we can increase our body’s natural cannabinoids. There are no big shockers, most are considered foundational in the naturopathic approach. 

  • Eat more omega-6 fatty acids (ie nuts, seeds, and olive oil) – these are the building blocks!
  • Exercise – this helps to increase both CBD1 receptors sensitivity and increase anandamide, which actives the CBD1 receptors. Interestingly, the motivation for exercise over eating, seems to be regulated by CBD1 receptors, at least in mice, but seems to be consistent to what we see in humans who use a lot of marijuana. CBD1 receptors diminish in the body with chronic marijuana usage…
  • Stress less – stress especially chronic stress reduces our CBD1 receptors
  • Cold exposure – Yes, the good old hydrotherapy practice of ending the shower with 30 seconds of cold water can help to increase endocannabinoid tone.
  • A nutritious diet, with adequate calcium, vitamin A, potassium, and folate will help to increase CBD1 expression and activation. Restricted diets can make getting these particular nutrients a challenge.
  • Get outside in the sun for at least 15 minutes per day – low level ultraviolet radiation exposure increase endocannabinoids in humans!
  • Cook with spices or consume teas with herbs, such as cinnamon, clove, black pepper, star anise, basil, mint, age thyme, and marjoram, all that contain beta-caryophyllene which actives CB2 receptors. Carrots contain some of this as well.
  • Balance your hormones. Testosterone, estradiol, and progesterone all help to increase the tone of the endocannabinoid system. Strength training is one of the best ways to help get these hormones back into balance for both men and women! 

Dr. Sarah Giardenelli is a naturopathic doctor, acupuncturist, and the owner of Collective Health Center. She is a proponent patient empowerment and enjoys the role as doctor as teacher, helping patients make informed lifestyle choices. Fill out the form below to learn more about us!

Editor's Note: This post was originally published in March 2019 and has since been updated for accuracy and comprehensiveness. 

 

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