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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Immune System Function Improved with 5 Steps

Immune System Function Improved with 5 Steps

by | Sep 6, 2019 | Herbal Medicine, Immune Health

Take care of your immune system starting with these simple steps. Dr.Sarah Giardenelli will teach you how to fend off the flu and bolster your immune system function.

1)  Lean on your herbal friends.

One of my favorites, I recommend patients’ keep on hand in their natural medicine cabinet for immune support is Elderberry, also known as Sambucus. Elderberry is an immune tonic that can be taken regularly during the fall and winter seasons for immune support or can be taken more often for acute colds and flu. Elderberry protects against the flu, helps to decrease inflammation, can help break fever, and tastes delicious in any form, tea, syrup, gummies, and even medicinal wines. Syrups are my favorite version of this as they are palatable for both kids and adults. There are many brands available, but my favorites are the high potency, low sugar options. A common practice in herbal medicine circles is homemaking elderberry syrup for the family, something to keep in mind next fall when the elderberries are ready for picking. Here is a link to herbalist Rosemary Gladstar’s elderberry syrup recipe.

Another well known, safe and easily accessible herbal used commonly for immune system support is echinacea. Some research indicates that Echinacea angustifolia may help to make the immune system response to the flu vaccine more effective, while other research demonstrates a cup of hot echinacea tea per day to be as effective as oseltamivir (aka Tamiflu) in reducing the symptoms of clinically diagnoses and virologically confirmed influenza virus infections, with less chance risk of complications and side effects.

2) Don’t forget the healing power of water.

Warming socks is an old school naturopathic approach to bolstering the immune system using contrast hydrotherapy or alternating hot and cold compresses. This can be done when feeling run down or when acutely ill with an upper respiratory infection. So effective is this in helping to make my hubby feel better when feeling run down or sick that he will initiate this himself and encourage me to do the same when I am run down. The procedure involves these few simple steps: 1) Warm up your feet for 5 to 10 minutes, quickly done by soaking them in warm water; 2) Take a pair of knee high cotton socks and soak them in cold water and wring them out thoroughly; 3) Place the cold wet socks over your warm feet and then cover these wet socks with thick wool socks.; 4) Go to bed and avoid getting chilled.

3) What about supplements?

Probiotics generally enhance natural immunity and some specific strains of Bifidobateria and Lactobacillus strains show benefit in the prevention and treatment of influenza.  A daily probiotic supplement in school children appears to reduce both incidence, symptoms of cold and influenza, and helps to decrease frequency of antibiotic prescription. (3)

There is controversary about vitamin D supplementation in preventing influenza, with conflicting results from research. Well designed studies do not indicate high doses have any preventative effect from influenza and high doses can increase levels of calcium in the blood stream, which can be problematic for cardiovascular, brain, and kidney health. So getting levels checked and treading cautiously with vitamin D is recommended. Genetics have a lot to do with need of vitamin D, and can inform and will likely help inform more personalized dosing guidelines for vitamin D in the future. Given this, I have steered away from recommending high doses of vitamin D for most patients without compelling reason. (3)

Studies on vitamin C show just a slight reduction in length and severity of colds. (3)

4) Immune boost your nutrition.

We known that sugar suppresses immune function, so limiting any added sugars as much as possible is generally encouraged for both preventing and recovering from illness. Encouraging balance blood sugar with a diet that is lean and green is also recommended to support general health.

Garlic is traditionally known for its immune protective benefits. Supplementation for 90 days with aged garlic extract has demonstrated effect in reducing the severity of symptoms, duration of illness, and frequency of colds and flu. (3)

Food grade mushrooms such as, oysters, shiitake, turkey tail, and portobellos, are high in beta-glucans which have demonstrated immunomodulatory, anti-inflammatory, and have anti-microbial effects. Studies on supplementation with beta-glucans from mushrooms or yeast have demonstrated effect in managing respiratory tract infections in children and adults. (2)

 5) Be positive.

I love that we can modulate our immune and overall health with our minds and l LOVE that I get to help patients capitalize upon this to benefit their health. And I am thrilled, that I have come across this recent small study on older adults that demonstrates that positive mood either daily in the 6 weeks prior to vaccination or on the day of vaccination, significantly predicted greater antibody responses to influenza vaccination (H1N1 strain). The effect of positive mood was the only factor found to significantly predict great antibody responses to influenza vaccine over age, gender, daily steps, sleep, caloric intake, or recommended daily intakes of zinc, vitamin A or vitamin E. This was the first study of its type “to comprehensively examine patient behaviors and psychological factors on the vaccine-induced protective antibody response in older adults using a robust methodology (prospective, diary-based longitudinal study)”. (1) I hope that this effect will be researched further in larger studies that evaluate the overall effectiveness of vaccination in those with positive mood. This effect would be interesting to see evaluated in other types of vaccination, like immunotherapy (allergy shots or drops).

In fact, all aspects of our lifestyle: physical activity, sleep, stress, and mood have been identified as immune modulators that impact vaccine response or effectiveness.(1) Something keep in mind obviously not just prior to any vaccination, but on a daily regular basis, is minding and caring for yourself and reducing stress through either over activity or inactivity, getting adequate sleep, eating a balanced diet low in added sugar, and keeping a positive outlook all help prevent us from getting ill in the first place.

Dr. Sarah Giardenelli is a Naturopathic Doctor & Acupuncturist at her private practice, Collective Health Center, in Leesburg, Virginia. Dr. Sarah specializes in a caring and out of the box approach to optimizing health and reversing chronic disease using natural medicine. More information on Dr. Sarah’s practice can be found at www.collectivehealthcenter.com.

References

1) Ayling et al. Positive mood on the day of influenza vaccination predicts vaccine effectiveness: A prospective observational cohort study. Brain Behav Immun. 2018 Jan;67:314-323. https://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+28923405

2) Jesenak, M., Urbancikova, I., & Banovcin, P. (2017). Respiratory Tract Infections and the Role of Biologically Active Polysaccharides in Their Management and Prevention. Nutrients, 9(7), 779. https://www.ncbi.nlm.nih.gov/pubmed/28726737

3) Mousa, HA. Prevention and Treatment of Influenza, Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural Therapies. J Evid Based Complementary Altern Med. 2017 Jan; 22(1): 166–174. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871211/#bibr76-2156587216641831

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Mental Health is Heart Health

Mental Health is Heart Health

by | Aug 9, 2019 | Cardiovascular Health, Chinese Medicine, Herbal Medicine, Stress Management

Mental health is heart health. Heart ache can literally cause “takstubo cardiomyopathy” or heartbreak syndrome, this presents similarly to a heart attack, and thankfully occurs very rarely, when stress hormones severely spike, such as the loss of a loved one or when otherwise in extreme duress.

One of the beautiful aspects in both naturopathic and Chinese medicine is that it considers and addresses both the physical and mental health factors of disease. Rose flowers are one of my favorite herbs for trauma, they both clear heat and calm the spirit. In Chinese medicine, our spirit or shen, is thought to reside in the heart and the heart is thought to control all the other organ systems. So any extreme emotional disharmony can cause imbalance in all of the other organ systems. 

 Asking for help to improve your mental health

The most devastating time in my life was loosing my mother-in-law, Barbara, to a drunk driver. However, I am grateful for what this terrible time in my life taught me. It was a few years of coming back into myself and working on my mental health. It took asking for help. Accepting that help. Prayer. Moving on from regrets. Self-care. And of course an awesome naturopathic doctor.

This is the personalized care naturopathic and Chinese medicine offers. It goes beyond functional medicine into truly dynamic, bioenergetic care. Sure, I can help to lower those elevated cholesterol, hs-CRP, homocysteine using lifestyle, nutrients and herbals. However, my passion is getting to the heart of the matter. 

Custom treatments for physical and mental health

Working with my patients at a personal and relational level. Through this work we get a truly personalized approach and this enables me to do things like customize herbal formulas for my patients based non only on their totality of their symptoms, but their constitutional picture, including their mental health. Even if I use a single herb, I am always thinking about how that herb will support the patient at these deeper levels.

The heart might stay scarred, but for this mine is stronger, and I am blessed to use this learning to help others.

Dr. Sarah Giardenelli specializes in integrating both Naturopathic and Chinese medicine to provide the best possible care for each patient. If you are interested in learning more please fill out the form below. Dr. Giardenelli's office is located in Leesburg, VA in the Leesburg Junction building.  

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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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