Biological Aging vs. Chronobiological Age – An Important Role for the Mitochondria, Part 2

Professor Serge Jurasunas, MD(hc), ND, MD(Hom)


Introduction

Can we increase healthy lifespan and slow down age-related diseases in the elderly using nutritional factors? Everyone ages; but depending on many factors, aging can be delayed or accelerated. In recent decades, research has focused heavily on the processes of aging to reveal potential targets for prolonging health and lifespan. Several factors associated with a healthy lifespan and against aging include a food diet, low caloric restriction, lifestyle, exercise, and meditation.1-4 

There is also growing evidence regarding the therapeutic potential of natural compounds that can restore mitochondrial function and promote healthy aging.5,6 I learned much about nutrition and aging with Dr. Bernard Jensen, one of the greatest pioneers in nutrition of the past century when I met him over 60 years ago. I spent much time at his Hidden Valley Health Center and kept in close contact with Dr. Jensen until its death.


Food Diet and Healthy Lifespan

Food diet has been shown to increase healthy lifespan up to 100 years of age and, more often, without the common diseases of the western world. There is a huge difference between the health status of average people in modern society and healthy people, especially centenarians from different countries such as Okinawa. The difference is associated with food style, lifestyle, and philosophy of food.

Our western food style is based on industrially transformed food with its excess of bad fat, sugar, salt, animal proteins, etc. and which contain much fewer nutrients and health benefits. For instance, our immune system needs a battery of nutrients to be correctly activated, so as we age the immune defense is less efficient; healthy food and nutrition play a key role by enhancing immunity in aging.7  Most  elderly lack nutrients and their immune defense has lost efficacy resulting in increased vulnerability to disease, infection, cancer, and susceptibility to an age-related inflammatory reaction.  An American study published in the Lancet magazine, in November 1992, concluded that elderly people are deficient in vitamins and trace elements and have a decrease in their immune defense.8

Today science is making a very serious study about two typical models of food diet that increase healthy lifespan and prevent diseases such as heart and cancer. We know that vegetables, fruits, and whole grains are important in our daily diet; yet a recent US Center for Disease Control and Prevention (CDC) study found that only 12% of adults consume 1-1/2 cups of fruit each and only 10% of Americans eat the recommended 2 to 3 cups of vegetables each day, including legumes.

About 50% of grain consumption should be whole grains, yet over 95% of Americans fail to meet that goal, instead eating processed grains that have been milled to remove the grain, bran, and many nutrients, including fiber. Over 50% of Americans fail to eat the 5 grams (a teaspoon) of recommended nuts and seeds each day; we know how walnuts, for example, are important for good brain function. With wrong food intake year after year, we push our bodies to premature aging and age-related disease.

According to a recently published new study, if a woman began eating optimally at 20 years of age she could increase her lifespan by over 10 years and a man could add 13 years to his life. What is interesting to note in this study is by starting at 60 years of age, a woman could increase her healthy lifespan by eight years; and even at 80 years of age, changing to a better diet would improve her health condition.

During my lifetime practice, I was lucky to accompany patients for a period of up to 48 years. In 1983, I treated a seven-year-old boy with a huge 7 cm Wilm’s tumor with no surgery or chemotherapy and the family started to change their food style. Today the boy is a 43-year-old man and still healthy.  Some of the oldest patients that I treated over several decades are today 87 years of age, with good physical appearance and brain function.  One of my patients, today a 79-year-old female, came to see me for the first time in 2008. She complained of serious cognitive disorders such as loss of orientation, and very poor memory on the way to Alzheimer’s disease; but in 2022 after 14 years, she is none the worse, even physically feeling much better from following my dietary advice and supplementation.


The Okinawa Food Model

This model is quite similar to the healthy Mediterranean diet except for a few different foods from the Japanese such as olive oil, capers, green pepper, goat cheese, fermented milk, etc. Okinawan food is a good model of food style leading to healthy aging and longer lifespan since natives live over 100 years of age and keep working in fields at an advanced age.9 According to scientific studies, the maximum life span in humans is 100 -120 years; however even now we have 150 years.10 Fauja Singh a British Indian, ran the Boston Marathon at 100 years old, then at 104 years the marathon in Bombay. Today at 111 years, Fauja does not run anymore because he suffers from a bad hernia but still walks 8 km per day.

The Okinawa model is based upon a diet rich in fruits, high fiber, and green and yellow vegetables all rich in antioxidants. It includes daikon radish (very rich in antioxidants), okra, pumpkin, sweet potatoes (also very rich in antioxidants), including wild vegetables, root vegetables, herbs, whole grains, mushrooms, seaweed such as fucoidan, millet, noodles, and only a little rice. They consume tofu, natto, miso, seitan, fish, and a small quantity of meat. They use no saturated fats, sugar, or processed foods.

Figure #1: Okinawa Food Pyramid

Vegetables: 58%-60%

Grain: (33%)

Soy food: (5%)

Meat and seafood: (1-2%)

Fat: no saturated fat (6%)

Okinawans have a low protein and high carb diet and much less protein with a ratio of 10-1. They follow a diet based on low calories but rich in nutrients,11 so the body is less busy repairing damaged DNA and limits oxidative stress. In fact, this whole diet model is very rich in antioxidants, polyphenols, anthocyanins, quercetin, lycopene, selenium, vitamins, minerals, enzymes, etc., that help keep cells and mitochondria young and healthy—helping further to slow down or reverse the aging clock.  Japan has the highest life expectancy of any country, with 90 years for women and 80 years for men.12,13 Okinawa has 400 centenarians.


List of the Best Anti-Aging Foods

Figure #2: Okinawan Typical Diet

Broccoli, avocado, pumpkin, nuts, red and yellow peppers, watercress, carrots, pomegranate, red onions, grapes, virgin 100% cold pressed olive oil, virgin walnut oil, beets, sweet potatoes garlic, red onions, daikon radish, yellow and green peppers, artichokes, fermented garlic, black garlic, mushrooms, sprouted vegetables, and seaweed. Other important foods include black and red rice, red and black quinoa, lentils, millet, barley, chickpeas, sesame foods, and chia seeds, all rich in vitamins, minerals, and proteins.

Anti-aging foods that also feed your microbiome include tofu, miso, natto, kombucha, fermented foods like sauerkraut or red beets, kefir, and buttermilk. Reduce the intake of red meat that damages the good bacteria of your microbiome and favors bad bacteria.

According to Nobel Laureate (1908) Elie Metchnikoff, bacteriologist and immunologist, there is a link between gut microbes and the intake of fermented foods, fermented milk, fresh vegetables, and fruits, to health and longevity.14 According to him, toxic bacteria and auto-intoxication of the colon are associated with mental health and the aging process, but good bacteria and lactic acid bacteria can increase lifespan with better health.15 The microbiome composition changes with chronological age, but lifestyle and food style can balance the gut microbiome and thus may contribute to the good health of an aging person. 

According to researchers, food style and environmental effects on the microbiome can delay or accelerate unhealthy aging.16 The gut changes as the host ages, being altered according to the food style and age-related diseases. According to a new study done by Chinese with a  cohort of more than 1,000 healthy Chinese individuals ranging in age from 3 to 100 years, surprisingly they found that the overall microbe composition of the healthy aged group was similar to that of people decades younger.17 They speculated that this similarity is a direct consequence of a healthy lifestyle and diet since in some provinces Chinese natives eat a food diet almost similar to the people in Okinawa.

Now lifestyle-linked factors such as diet, stress, and meditation influence the aging process but also the gut.  In older people, the gut microbiome deteriorates so it needs some combined approaches, including dietary intervention. The Okinawan diet follows low calories with a rule not to eat over indulgently but to finish a meal when the stomach is only 80% full and not 100%.18 This is similar to low-calorie diets that are now widely accepted as a factor that increases lifespan. Calorie restriction is a potent modulator of longevity in multiple species, including rats and macaques. Low-calorie does not mean lower nutrients; to the contrary, natural food and organic vegetables contain more nutrients.

Emerging evidence suggests that numerous biologically active compounds alone or combined may be beneficial to improve age-related decline with specific benefits on mitochondria function by increasing the respiratory chain, decreasing ROS activity, and substantially increasing free ATP level production. Restoration of the gut microbiome is also a major step since it modulates the immune system and its associates with aging.

To conclude we cannot neglect the intoxicated colon and wrong foods that produce excess toxins that I mentioned in part I (see February 25, 2023 Townsend e-Letter). With aging and decreasing levels of detox enzymes, such as glutathione, for instance, toxins and chemicals build up within the body, tissues, and intoxicate cells and even mitochondria since intoxicated blood carries not only oxygen but also toxins to mitochondria.


Supplements and Natural Compounds That Increase Mitochondrial Function and Help You Maintain Healthier Aging

Coenzyme Q10: Co-Q10 plays a vital role in the production of chemical energy ATP in mitochondria. Co-Q10 is an essential component of the mitochondrial transport chain located in the inner membrane and is an essential carrier to transfer electrons between complexes I, II, and III of the mitochondrial respiratory chain. Deficiency causes a decline in activities of complexes II+III and complex V.

Co-Q10 reduction occurs during the aging process but supplementation can delay or restore functional decline, particularly regarding Parkinson’s disease since Co-Q10 deficiency was observed at a higher frequency in Parkinson’s disease.19,20 Co-Q10 also works as a potent lipid-soluble antioxidant and therefore plays a key role in mitochondria against the deleterious effect of ROS. One of the essential targets of Co-Q10 is to protect the heart against failure and to reduce cardiovascular mortality especially.21 

A new important study from Scandinavian researchers was the first population-based study measuring the effect of long-term intervention with a combined of CoQ10 (200 mg per day and selenium (200 micrograms per day) during 42 months preserved telomere length and prevented cardiovascular mortality, as I have explained in part I of the article. Less telomere shortening during the following period was associated with significantly longer survival.22,23 Overall Co-Q10 is highly indicated not only to retard age-related disease but as a possible treatment for neurodegenerative disease.24 Supplementation can delay functional decline, particularly in Parkinson’s Disease. In part one related to pregnant women and oocytes that concentrate in a high number of mitochondria, it has been shown that Co-Q10 restores the mitochondrial function and thus improves fertility and combats aging that may start in the embryo.25

NADH (Nicotinamide adenine dinucleotide)  is a high-energy electron carrier found in every cell and is critical to boosting the production of ATP and DNA repair.  NADH starts at complex I for the transport of electrons generated by the Krebs cycle and the electron transport chain. The more NADH a cell has available, the more ATP is produced. NADH supplementation leads to an extension of the lifespan and vitality of cells, tissues, and organs. NADH, which is also a strong antioxidant, possibly slows down and restores some function in diseases such as Parkinson’s, amyotrophic lateral sclerosis, and Alzheimer’s disease. NADH declines with age and is associated with physical and brain decline.

It was the Austrian researcher, George Birkmayer who discovered the therapeutic value of NADH and managed to have it synthesized in supplement form under the brand name ENADA. When I first met him many years ago at his Institute for Parkinson’s Therapy in Vienna, he already had successfully treated Parkinson’s disease even at its advanced stages.26

Curcumin, well-known for its anti-cancer properties is also very useful for the brain, being first a strong antioxidant with anti-inflammatory properties and may have a good effect on healthy aging and Alzheimer’s disease.27 Curcumin decreases beta amyloid plaques,28 delays the degradation of neurons, and decreases lipid peroxidation and microglia formation. Overall memory in patients with Alzheimer’s disease has improved when taking curcumin. Curcumin is considered an anti-aging factor and increases lifespan in several species.29,30 In other studies, curcumin was able to extend the lifespan of such organisms as fruit flies and mice, alleviating symptoms of some diseases including age-related ones.

Pyrroloquinoline quinone (PQQ): A very important molecule found in mammalian tissues associated with various biological processes has received an increasing amount of attention because of several health benefits, mostly attributed to its ability to enhance mitochondrial biogenesis31 and increase the NADH level, therefore playing a major role in the aging process. PQQ is also known to act as a powerful antioxidant, more efficient than any other antioxidant, and protects mitochondria against ROS activity.

However, PQQ is more than an antioxidant. PQQ has potential health benefits, such as improved metabolic flexibility and immune and neuroprotection when associated with dietary supplementation. PQQ may act vitamin-like, with strong potential as a potent therapeutic nutraceutical.32 Daily supplementation with 20 mg PQQ optimizes mitochondrial biogenesis in human subjects; notably cognitive function and memory are also improved.33 What makes an enormous difference from other compounds is the fact that PQQ can modulate the quantity and function of new mitochondria, especially in aged cells.34

It is interesting to note that PQQ could be necessary for the life of eukaryotes cells on this planet since NASA identified PQQ as a component of interstellar dust. It may have been present throughout the early biological conception and evolution of life on the planet. Several foods and anti-aging fermented foods that we have suggested such as tofu and natto are rich in PQQ, along with kiwi, papaya, green pepper, green tea, and parsley (very rich in PQQ).35 However, natto is the richest source.35  PQQ supplementation is suggested for more easy intake but it’s been shown that natural food is fundamental for our good health status.

Resveratrol is a natural phenolic compound exclusively found in more than 70 species of fruits and vegetables such as blueberries, strawberries, grapes, peanuts, etc., demonstrating many physiological effects in laboratory animals, including immunomodulatory, anti-inflammatory, and antioxidant. Resveratrol is efficient in the prevention and management of neurodegenerative disease, cancer, diabetes, obesity, osteoporosis, and cardiovascular disease.36,37 Cumulative studies revealed that resveratrol could extend lifespan and extend healthy aging.38

Resveratrol exerts many effects in the body such as relieving inflammatory reactions, improving mitochondria function by scavenging ROS activity and decreasing oxidative stress throughout, and inducing higher levels of SOD1, SOD2, catalase, and GXP activity.39,40 In fact,  resveratrol can inhibit the formation of ROS that can gradually compromise the structures and function of cells giving rise to cell senescence and accelerating aging thus exerting anti-aging effects. Resveratrol exerts a direct effect on mitochondria by inducing the expression of nuclear-encoded genes for mitochondrial biogenesis.

Resveratrol has neuroprotective effects in neurovegetative diseases. In some preclinical studies, resveratrol decreases the amount of beta-amyloid protein in the cells that grow in the lab and the brain of mice promoting the breakdown of the protein and protecting against Alzheimer’s  disease or retard symptoms.41,42 Now one of the well-known actions of resveratrol is to mimic the effect of a restricting caloric diet by activating a class of enzymes known as sirtuin (SRIT1) that is expressed in the adult mammalian brain, predominantly in the neurons.

Figure #3: Microbiome Modulates Mitochondria

Sirtuins are a class of nicotinamide adenine dinucleotide (NAD) consuming enzymes that are implicated in numerous pathways, originally the subject of studies of the lifespan-extending gene. Deregulation of sirtuins links to disorders in mitochondrial function and has been implicated in various diseases such as neurodegeneration and cardiovascular disease.43 When overexpressed, sirtuins play an important role in neural protection as it regulates ROS, pro-inflammatory cytokines, and AB peptides and expression in the brain of AD patients.44 

Activation of sirtuins by resveratrol may prevent AB peptide-induced microglial death and contribute to improved cognitive function.45 Besides protecting the neurons, sirtuins control the biogenesis of the metabolism of mitochondria; and resveratrol has the same effect.46 A low-calorie restriction appears to activate sirtuins, and resveratrol supplementation mimics the same effect increasing energy metabolism.47 Thus sirtuins mediate beneficial effects elicited by such diets. Okinawans follow a calorie-restricted diet and have 40% more centenarians and much less sickness than the rest of Japan. Calorie restriction delays or prevents age-related disease and extends lifespan in several species, and quality of life in humans. It also contributes to increased lifespan in such animals as mice and monkeys.45,46

Some studies found that microbiota dysbiosis is found to be closely related to neurodegenerative disease (Shen et al 2017).  Accumulated studies show an interaction between resveratrol and the gut microbiota. Now besides mitochondria being one of the most important factors of aging, the gut microbiome is also known to modulate healthy aging.47-49 In older people, the gut microbiome deteriorates; although, in healthy aged people, the gut microbiome is similar to one of younger ones (see reference 17). The gut microbiota composition is shaped by diet in healthy elderly.50,51 Dietary intervention with resveratrol supplementation is mostly indicated as routine in healthy life or for an aged person as an anti-aging intervention.51 Resveratrol can definitely protect us from several age-related diseases and extend our lifespan. Overall, resveratrol modulates mitochondrial function and biogenesis, protects against neurodegenerative disease and cardiovascular disease, retards the aging process, and extends lifespan.

Ergothioneine (EGT): Ergothioneine is an amino acid and powerful antioxidant52,53 with several physiological properties found specifically in mushrooms that I have listed as important anti-aging foods. According to researchers at Penn State University USA, the high amount of EGT and glutathione in mushrooms give them anti-aging potential; however, EGT has a stronger effect to scavenge free radicals compared to glutathione or other conventional antioxidants.52

Two portions or more of mushrooms a week reduce mild-cognitive impact by 43%. One of the effects of EGT is to concentrate in mitochondria and accumulate in the brain through the OCTN1 transporter, which makes it particularly effective to protect from cognitive disorder and age-related disease, but also accumulate in other organs that need antioxidants against oxidative stress. Recent studies done in Singapore found that eating mushrooms more than two times a week contributes to improving the cognitive levels and extending the life of patients.53 In the elderly, especially in patients with neurodegenerative disease, the level of EGT is significantly decreased in the brain and plasma.54

One other important action of EGT is to protect from the shortening of telomeres,55 thus preventing early aging. Naturally, however, EGT levels in whole blood and plasma decrease with age, which is considered to be related to a change in dietary habits. This predicts cognitive and functional decline.56 The country with the lowest intake of EGT is the USA,57 which has a lower average life expectancy compared to Italians who ingest more than a four times greater amount of EGT daily.

Plants don’t synthesize EGT, and neither can the body; but mushrooms contain high levels of EGT that vary between different mushroom species, thus it is suggested that EGT supplementation from mushroom extracts might be necessary to maintain neuronal cell function and prevent neurodegeneration to some extent.

Many other natural compounds have demonstrated similar effects to prevent or reduce cognitive disorders and anti-aging properties. These include quercetin, anthocyanins, lycopene, catechins, alpha lipoic acid, Ginkgo biloba, green tea, EGCG, genistein, apigenin, melatonin, etc. However, to keep healthy while aging, I do believe that first we change our dietary style and introduce new conceptions or philosophies in our life. There are some new rules we can introduce in our daily lifestyle and food style, and this is what I teach to my patients. However, I do believe that dietary supplementation can help to support the body against age-related diseases.

Here is the list of combination supplements that reinforce their efficacy, according to the need.

  • Co-Q10+selenium. (protection of the length of the telomeres)
  • Co-Q10+PQQ. (to increase the number of new mitochondria)
  • Co-Q10+NADH. (prevention or delay of Parkinson’s symptoms)
  • Co-Q10+resveratrol. (for cardiovascular disease or protection)
  • Co-Q10+curcumin. (protection or delay Alzheimer!s disease)
  • Curcumin+resveratrol+NADH. (prevention or delay cognitive disorder in Alzheimer’s disease)
  • Curcumin+melatonin. (increases the expression of the level of complexes I, II, and V in the ETC of mitochondria.
  • EGT+NADH.(Anti-aging potential, cognitive disorder)

Of course, we need high-quality supplements, which means choosing wisely among so many available companies online. My favorite ones for quality are from Now, Thorne, Doctor’s Best, or Allergy Research Group.

Published March 11, 2023


References

  1. Buettner, Dan 2015. The blue zone solution. Eating and living like the world’s healthy people. National Geographic. ISB. N 978. 14262-1198.
  2. Carter G.D, Hepple RT, Bamman MM and Zierath JR. (2016) Exercise Promotes Healthy Aging and Skeletal Muscles. Cell Metab. 23-1034-1047.
  3. Daniela Sormenta et al. Physical exercise. A novel Toll to protect mitochondria. Frontiers in Physiology. 27 April 2021.
  4. Elissa Epel Ph.D., Jennifer Danbenmier Ph.D., and Elizabeth Backburn Ph.D. Can meditation slow the rate of cellular aging? Cognitive stress, mindfulness and telomeres. Annuals of the New York Academy of Sciences. 2011, March 11
  5. Diego Arauna. Maria Furrianca, Ivan Palonio. Natural Bioactive compounds as protector of mitochondrial dysfunction in cardiovascular diseases and aging. Molecules. 2019. 24 (23) 4259.
  6. Halibur Rahman, Johnny Bajal et al. Therapeutic Potential of Natural Products in Treating Neurodegenerative Disorders and Their Future Prospects and Challenges. Molecules. 2021.26 (17) 5327.
  7. Pae M, S. Nikibin. Meydani Dayong Wu. The role of nutrition in enhancing immunity in aging. Aging Dis. (2012) 391-100.
  8. RK Chandra. Effects of vitamins and trace elements supplementation on immune responses and infections in elderly peoples. Lancet. Vol 140. issue 8828. 1124-1127. 17 Nov.1992.
  9. Ansley Hill. What is the Okinawa Diet? Foods, Longevity, and more. RD. LD on April 16. 2019.
  10. Emily Willingham. Humans could live up to 150 years. New Research suggests. Scientific American. May 25, 2021.
  11. D. Grong, Wellcox, et al. (2009) The Okinawan Diet, health implications of a low calorie, Nutrient Dense, Antioxidant. Rich Dietary Pattern, low in glycemic food. Journal of the American College of Nutrition.28. 500S-516S.
  12. Shoichiro Tsugane. Why has Japan become the world’s most long-lived country? Insight from a food and nutrition perspective. European Journal of Clinical Nutrition. 75-921-928. (2021)
  13. Dr. Martin Juneour MD. Why do the Japanese have the highest life expectancy in the world? (cardiologist and director of prevention, Montreal Heart Institute, Faculty of Medicine. University of Montreal, 9 March 2021.
  14. Podolsky SH.  Metchnikoff, and the Microbiome. The Lancet. Nov 24-2012.
  15. Tarni Shankar, Ghosh, Ferrous Shenakan, Paul V O’Toole. The gut microbiome as a modulator of Healthy aging. Nature Reviews. Gastroenterology x Hepatology. 19-565-584 (2012)
  16. Lax S, et al., Longitudinal analysis of microbial interaction between human and the inborn environment. Science. 345. 1048-1052 (2014)
  17. Bian G, et al. The gut microbiota of healthy Age Chinese is similar to that of the healthy young. M Sphere. 2017. Sept 27. 2 (5) 00327-17
  18. D Craig Wilcox et al. (2009)  The Okinawa Diet. Health implication of a low calories Nutrients. Dense, Antioxidant, Rich Dietary Pattern, low in glycemic load. Journal of the American College of Nutrition. 28-500S-516S.
  19. Felix Javier, et al. Coenzyme Q10 and Parkinsonian syndromes. A systematic Review. Journal of `personalized Medicine. June 12, 2022; (6) 975.
  20. M. Barcenilaa B, et al. Serum levels of coenzyme Q10 in patients with Parkinson’s disease. J. Neural Transm. 2000; 107: 177-181.
  21. James J. Dinicolantonio, Jaikrut Bhutani, Mark F Mc Carthy, and James H O’Keefe.  Coenzyme Q10 for the treatment of heart failure. A review of the literature. Open Heart. Volume 2. issue 1. 7 August 2015.
  22. Tine Baur, O P Stas, Audess Larssen, Ingelbjorg Seljeflot and Urban Alehogen. Selenium and Coenzyme Q10 intervention Prevents Telomerase Attrition with Association with reduced cardiovascular Mortality. Sub Study of a Randomized Clinical Trial. Nutrients. June 2022. 14.3346.
  23. Abehogen U, Asaseth J, Alexander J, Johanson P. Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years- A validation of previous 10 years follow up results of a prospective randomized double-blind placebo-controlled trial in elderly. Plos One. 2018-13.
  24. Meredith Spindler et al. Coenzyme Q10 effects in neurodegenerative disease. Neuropsychiatric Disease and Treatment. 9 Nov. 2009. Vol 2009. 597-610.
  25. Koumei Shirasuna, Hisataka Iwata. Effect of aging on the female reproductive function. Contraception and Reproductive Medicine. 2 (23) 3 Oct 2017.
  26. JG Burkmayer C, Vrecko, D, Vole. Nicotinamide adenine dinucleotide (NADH)- a new therapeutic approach to Parkinson’s disease. Acta Neurol Scand suppl. 146.32-35.
  27. SD Voulgaropenlou, TAMJ Van Armelswoart, J Prickarets. C Vinherhoets. The effect of curcumin on Alzheimer’s disease and healthy aging. A systematic review of pre-clinical and clinical studies. Brain-Research. 15 Dec 2019;volume 1225;146-176.
  28. Fusheng Yan et al. Curcumin inhibits the formation of amyloid beta oligomers and fibrils binds plaques, and reduces amyloid in vivo. J. Biol Chem. Feb 2005. volume 280. issue 7.
  29. Alsane Bakrami, Fabrizio Montecucco, Federico Carbone and Amirhossein Sahelkar. Effect of curcumin on aging. Molecular Mechanisms and Experimental Evidence. BioMed. Res Int. volume 2021. Article ID 897-2074.
  30. Kyu Sun et al. Curcumin extends lifespan, improves health span, and modulated the expression of age-associated aging genes in Drosophila melanogaster.  Rejuvenation Research. Vol 3. N5  9 Dec 2010.
  31. Chowanadisai W. Bauerly K, Tchapareau E, et al. Pyrroloquinoline quinone (PQQ) stimulates mitochondrial biogenesis. FASEB. J. 2007-21-854.
  32. Karen R, Jonscheer, Winyoo Chowanadia and Robert B. Pyrroloquinoline quinone is more than an antioxidant-A vitaminlike accessory Factor important in Health and Disease. Prevention Biomolecule. 2021. Oct 11 (10) 1441.
  33. Shiojuana Y, Takahashi M, Takahashi R. Effects of dietary pyrroloquinoline quinone disodium salt on cognitive function in Health volunteers. A randomizes double-blind placebo-controlled, parallel-group study. Journal American Nutrition Ass. vol 41.2002. issue 8.
  34. Stites T, Storms D, Banerly K et al. Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice. J. Nutri. 2006. 136. 390-396.
  35. Taakeshi Kumazuwa. Levels of Pyrroloquinoline quinone in various foods. Biochem. J (1995) 367-333.
  36. A Saduzzaman Klan, Han-Ohum Chen and Dian-Zheng Zhong. Regulatory Effects of Resveratrol on Antioxidant Enzymes. A Mechanism of Growth Inhibition and Apoptosis induction in Cancer cells. Mol Cells 2013. April 30-35 (4) 355.
  37. Bui Thank Tung, Elisabet Rodrigues-Bies. Modulation of Endogenous Antioxidant Activity by Resveratrol and Exercise in Mouse Liver is Age-dependent. J. Of Gerontology series A. volume 69, issue 4 April 2014. 398-409.
  38. Philippe Maramand, Peter Davis. Resveratrol promotes clearance of Alzheimer’s Disease Amyloid B peptides. J. of Biology Chemotherapy vol 280. issue 45. 11 Nov 2005. 37377-37383.
  39. Karuppagonder SS, Pinto JT, Xu. H, Chen HL, Beaal MF, Gibson GE. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic model of Alzheimer’s disease. Neurochem. Int. 2009. 54 (2)  111-118.
  40. Pavithra Chandramowhishwaran. Anitha Vijoy. Role of sirtuins in modulating Neurodegeneration of the Enteric Nervous System and Central Nervous System. Front Neurosci. 2020.14 614331.
  41. J. Chen Y, Shon S, Mueller, Steiner, et al. SIRT1 protects against microglia-dependent amyloid B toxicity by inhibiting NFKB signaling. Journal of Biology Chemistry. Vol 280. N48.4036440374.
  42. Marambaud H, Zao and P. Pavies. Resveratrol promotes clearance of Alzheimer’s disease amyloid-B-peptides. Journal of Biological Chemistry. Vol. 280. N45. 37377-37382.
  43. Silvie Tuminers et al. Caloric Restrictions-like Effects on 30 days of Resveratrol supplementation on energy Metabolism and Metabolic Profile in Obese human. Cell Metabolism. Nov 2011;Vol 14 issues 52.: 612-627.
  44. Baur. JA. Resveratrol, sirtuis and the promotion of a Dr mimetic. Med Aging Dev. 2010. 131-261-269.
  45. Colman RJ, et al. Caloric restriction delay disease onset mortality in Rhesus monkeys. Science. 2009. 325-201-204.
  46. Ting-Ting Cai, Xiaa-Long Ye. Resveratol Modulates the Gut Microbiota in inflammation to protect Against Diabetic Nephropathy in Mice. Front Pharmacol. 19 August 2020.
  47. Tarini Shankar Ghosh, Fergus Shanahan, Paul W O’Toole. The Gut Microbiome as a Modulator of Healthy Aging. Nature Reviews Gastroenterology. 25 April 2022. 19-565-584.
  48. Claesson MJ, et al. Gut Microbiota composition correlates with diet and Health in elderly. Nature. 488-178-184. (2012).
  49. Vaiserman. AM. Kobrada AK. Marotta F. Gut Microbiota is a player in aging and a target for anti-aging intervention. Aging Research Reviews. 2017-35. 36-45.
  50. Chaplin A, Carpene C, Mercader J. (2018) Resveratrol, metabolic syndrome, and gut microbiota. Nutrients. 10 (11) 165.
  51. Akanamu D, Cechini R, Arnoma Q I and Halliweed B (1991) The antioxidant action of Ergothioneine. Arch Biochem Biophy. 288.10-16.
  52. F. Franzoni et al. An in vitro study of the free radical scavenging capacity of ergothioneine comparison with reduced glutathione, uric acid, and trolox. Biomed Pharmacother. 2006.Sept 6, (8) 453-7.
  53. Feng L, Cheak IK, Ng MM Li.J. Chan SM, Lim SL, et al. (2019) The association between mushroom consumption and Mild cognitive impairment. Community-based-Cross Sectional study in Singapore. J. Alzheimer’s Dis. 68. 197-203.
  54. Cheah IK, Feng L, Tang RMY, Halliwell B. Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline. A risk factor for neurodegeneration. Bloch-Biophy Research Communication. 9  Sept. 2016; Vol 478. Issue 1: 162-167.
  55. Priscilla Daniel, Menelanos Tsapekos Steven Chen. Ergothioneine mitigate Telomere shortening under oxidative stress condition. Journal of Dietary Supplements. Vol 19. 2022. Issue 2.
  56. Liu Yun Wu et al. Low plasma Ergothioneine Predicts cognitive and Functional Decline in an Elderly Cohort Attending Memory clinics. Antioxidants (Basel) 2002 Aug. 30.11 (9) 1717.
  57. Beelman BB, Kaloros M.D Phillips AT et al. Is ergothioneine a longevity vitamin limited in the American Diet? J. Nutr Sci. 11 Nov 2020.

Published March 11, 2023

About the Author

Serge Jurasunas is an internationally well-known practitioner and researcher in complementary oncology and molecular medicine, besides being a naturopath and a fervent believer in nutrition and detox since he met with Dr. Bernard Jensen in 1962. Member of the New York Academy of Science, Serge Jurasunas is a former professor at Capital University of Integrative Medicine in Washington D.C. and has devoted over five decades to treating all kinds of diseases and cancers of all types and grades. He is the author of eight books, including a new one Cancer Treatment Breakthrough-Immuno-Oncology using Rice Bran Arabinoxylan Compoundpublished in the US.  He is also an expert in germanium therapy for cancer treatment. His work and experience with germanium and cancer have been recently published in the Japan Medical Journal, “Effective Cancer Treatment Method” by Serge Jurasunas.

He has a large blog with many stories as well as articles in Slideshare. Serge Jurasunas is a frequent contributor to Townsend Letter since 1999 and maintains a private part-time practice only for cancer patients.

Contact information: sergejurasunas@gmail.com

Website: http://sergejurasunas.com/