Klotho, the Gene that Extends Lifespan and Increases IQ Return to Homepage

 

 

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The Klotho Gene Part #2. The ultimate Treasure map to Discovering the Secrets of Longevity.

I mention in my book Secrets to Creating Money Effortlessly using Lucid Dreaming, (currently undergoing a 2018 revision as of April 15th, 2018) the Terman study which is also known as the study of gifted people. This study is the oldest and longest-running longitudinal study in the field of psychology and was started by Lewis Terman at Stanford University during 1921 to track the lives of gifted children.  In 1990, a similar study was taken up by Dr. Friedman and Leslie Martin (Conscientiousness, Career Success, and Longevity: A Lifespan Analysis. et al. May 2009), (A follow-up of subjects scoring above 180 IQ in Terman's genetic studies of genius. Feldman, D. H.. 1984).

Their study concluded that conscientiousness and career success predicted longevity.  Other studies found the best childhood personality predictor of longevity was also conscientiousness (Conscientiousness and longevity: an examination of possible mediators. Hill PL et al. Sept 2011). ie; qualities of a well-organized, prudent and persistent person, much like a scientist-professor, somewhat obsessive and not at all carefree. Also conscientious people do not smoke and strive to live healthy lifestyles. The studies conducted  by Dr. Friedman found that genes constitute approximately one-third of the factors that lead to a long life. Hence, if your granddad lived to be 90, that does not say you will also live to 90.  Another study concluded that conscientious people have lower IQ's on average (Why is Conscientiousness negatively correlated with intelligence?Author links open overlay panel. Joanna Moutafi, et al. Oct 2004). \

This finding has since been confirmed by other studies

(A meta-analysis of the five-factor model of personality and academic performance". Psychological Bulletin. Poropat, A. (2009).  (Moutafi, J.; Furnham, A.; Crump, J. (2003). "Demographic and personality predictors of intelligence: A study using the NEO Personality Inventory and the Myers-Briggs Type Indicator". European Journal of Personality. 17: 79–94. doi:10.1002/per.471), (Moutafi, J.; Furnham, A.; Crump, J. (2003). "Demographic and personality predictors of intelligence: A study using the NEO Personality Inventory and the Myers-Briggs Type Indicator". European Journal of Personality. 17: 79–94. doi:10.1002/per.471.), (Moutafi, J.; Furnham, A.; Crump, J. (2006). "What facets of openness and conscientiousness predict fluid intelligence score?". Learning and Individual Differences. 16: 31–42. doi:10.1016/j.lindif.2005.06.003).

It is also important to point out here that there also exist a few studies showing higher IQ is linked to conscientiousness. More studies are needed to find the exact mechanisms for this relationship.
Reference
Intelligence and personality. Wikipedia.

Question
If conscientious people live longer, but have lower IQ's on average, what if there was a substance, herb, food or supplement that could do both?  IE: Lenghten lifespan and increase IQ at the same time?

 

A specific gene known as the Klotho gene enhances lifespan and may be able to answer this question.

Studies show that by stimulating this gene, that not only does it allow one to live longer, but it also increases a person's IQ in the process.

References
Article - Genes and intelligence. The 3% solution. The Economist. May 10th, 2014.

NIH Study - (Life extension factor klotho enhances cognition et al. Dena B. Dubal al. May 2014)

This is a very rare finding among numerous anti-aging formulas, as most will enhance mental alertness and preserve cognition, but not enhance IQ at the same time. Also many anti-aging substances, if taken in excess, increase one's chances of contracting cancer. Klotho, on the other hand exibits  anti-cancer properties (Klotho acts as a tumor suppressor in cancers. B. Xie et al. Oct 2013), (The Anti-Aging and Tumor Suppressor Protein Klotho.  Ci-Di Chen et al. June 2014).

 

Klotho enhances Superoxide Dismutase
I have written extensively in almost all of my anti-aging books that higher levels of superoxide dismutase and reduced levels of oxidative stress are 2 of the most potent methods to extend lifespan. Klotho has been shown to enhance manganese superoxide dismutase and reduce oxidative stress (Klotho enhances FoxO3-mediated manganese superoxide dismutase expression by negatively regulating PI3K/AKT pathway during tacrolimus-induced oxidative stress. Lim SW et al. August 2017). 

What is Superoxide Dismutase?
To put it in simple terms, superoxide dismutase is an enzyme that acts as an antioxidant to prevent damage caused by aging.  It is mostly generated by moderate exercise and exists in abundance when you are young.

What is Manganese superoxide dismutase?
Manganese superoxide dismutase transforms toxic superoxide into hydrogen peroxide and diatomic oxygen. (SOD2 superoxide dismutase 2 [ Homo sapiens (human) ]. Feb 2018). To put it simply, Managense superoxide dismutase, is a powerful toxin remover.

 

 

What is Klotho?
In humans, Klotho is also an enzyme that is encoded by the KL gene that was discovered in 1997 and it supresses several ageing phenotypes.  The name comes from Clotho in Greek mythology due to its relationship to the thread of life. The gene expresses itself  in organs and cells, such as the brain choroid and renal tubular cells. It is interesting to note that at the very start of many kidney diseases, disorders in the renal tubule will manifest.  Klotho activity varies with age.  From 0 to 10 years of age serum levels are low.  However from 21 to 40 years, it reaches a peak. After  a person reaches 40 years of age, the activity of their Klotho gene begins to decline (Role of Klotho in Aging, Phosphate Metabolism, and CKD. George B. John et al. April 2011) . When scientists removed Klotho from mice it resulted in the development of disorders associated with decreased longevity and human aging (Identification of novel small molecules that elevate Klotho expression. Gwendalyn D. King et al. June 2013).

 

The Klotho gene directly suppresses the gene responsible for aging (Molecular Basis of Klotho: From Gene to Function in Aging. Yuechi Xu and Zhongjie Sun. Feb 2015). Its effects are greatest in the kidney (Establishment of a cell-based assay to screen regulators for Klotho gene promoter. Zhi-liang XU.  et al. Sept 2004). It is interesting to note that the Tao states that the Kidneys are the region in the body that store what's known as 'Jing' which is recharged by practicing QI Gong type exercises.  This 'Jing' is strongest, or more in abundance in the body's kidneys, during the season of fall every year where it peaks in energy.  Ayurvedic medicine states that fall / autumn is governed by Pitta and late fall / autumn into winter is governed by Vata. We shall discuss the role Vata plays in greater detail later on.

Klotho Prevents Muscle Loss
Klotho has also been found to be important in the prevention of osteopenia, muscle atrophy and cardiovascular disease (Skeletal muscle as a regulator of the longevity protein, Klotho. Keith G. Avin et al. June 2014) and it enhances cognitive abilities, especially in women (KLOTHO genotype and cognitive ability in childhood and old age in the same individuals. IJ Deary et al. April 2005).

Klotho helps regenerate muscle - Quote from study - 'Moreover, we propose that Klotho may participate in the skeletal muscle regenerative cascade and that age-related declines in Klotho levels may contribute to the decreased ability of aged skeletal muscle to heal after injury'
Reference 
Skeletal muscle as a regulator of the longevity protein, Klotho. Keith G. Avin et al. June 2014.

The herb Fenugreek also builds muscle mass (The effects of a commercially available botanical supplement on strength, body composition, power output, and hormonal profiles in resistance-trained males. Chris Poole et al. Oct 2010).

Further Reading
Effects of Combined Creatine Plus Fenugreek Extract vs. Creatine Plus Carbohydrate Supplementation on Resistance Training Adaptations. Lem Taylor et al. June 2011.

Additional facts about Klotho -
Klotho likes to conregate in the body's fluids. Hence it can be obtained from the body's cerebro-spinal fluid, blood and urine (Association between Decreased Klotho Blood Levels and Organic Growth Hormone Deficiency in Children with Growth Impairment. Ido Wolf et al. Sept 2014).

Klotho increases intelligence by as much as 3% or 6 points. This was proven in a study led by Dena Dubal of the University of California and Lennart Mucke of the Gladstone Institutes  in San Francisco. Besides reducing heart disease, they found that when the Klotho gene was stimulated, that it boosed the cognitive faculties in both the young and old by the equivalent of about six IQ points.

References
Article - Genes and intelligence. The 3% solution. The Economist. May 10th, 2014.

NIH Study - (Life extension factor klotho enhances cognition et al. Dena B. Dubal al. May 2014)

Further Reading
Life Extension Factor Klotho Prevents Mortality and Enhances Cognition in hAPP Transgenic Mice. Dena B. Dubal et al. Feb 2015

The Mind and the Body
After writing thousands of pages about anti-aging and numerous anti-aging books over the years, and having developed numerous anti-aging formulas, which I have published in these books, and published some of the best in my report titled: Anti-Aging Longevity and Memory Enhancement Nutraceutical Herbal Combinations,  the latest available research is showing that herbs, extracts, pharmaceuticals and substances that strengthen the mind, many of which relieve depression, happen to be some of the most powerful anti-aging substances.  My own very latest research has found that research studies are now showing that certain coherence exercises such as HeartMath, when done properly have more profound effects upon the body then the herbs themselves.  This I shall write about in an upcoming article.  But the underlying theme is that the mind has the power to heal the body and more-so when it is in coherence with the heart (HeartMath).

 

 

Astragalus and its Protective Cognition Properties
As just discussed, Klotho has been shown to enhance the brain's cognitive abilities. Another substance that helps protect the brain's cognitive abilities is the chinese herb Astragalus. A research study found that a combination of dexamethasone with Astragalus significantly improved learning and memory in mice (Protective effect of extract of Astragalus on learning and memory impairments and neurons' apoptosis induced by glucocorticoids in 12-month-old male mice. Li WZ et al. June 2010). Another study found that the components  Epimedium, Astragalus and Radix Puerariae reduced cognitive deficits, reversed Aß burden,  inhibited Aß plaque accumulation and reduced the brain iron load in mice (Neuroprotective effect of the active components of three Chinese herbs on brain iron load in a mouse model of Alzheimer’s diseaseXIAN-HUI DONG) et al. Jan 2015. 

A common herbal alternative to the prescription only substance dexamethasone is liquorice root and astragalus, which when used together have been found to boost superoxide dismutase levels in yellow perch (Feeding Glycyrrhiza glabra (liquorice) and Astragalus membranaceus (AM) alters innate immune and physiological responses in yellow perch (Perca flavescens).Elabd H et al. July 2016). Another alternative is Boswellia papyrifera (Better the Devil you Know? ‘Boswellia serrata’ as an alternative to ‘Dexamethasone’ to treat peritumoural oedema. Kylie Wright, Liverpool Hospital, NSW. Australia), which has been shown to help treat cognitive impairment in people who have multiple sclerosis (Effect of Boswellia papyrifera on cognitive impairment in multiple sclerosis. Behnaz Sedighi et al.  July 2014)

 

 

 

 

Further Reading

 

 

Temporary anti-cancer & anti-pain effects of mechanical stimulation of any one of 3 front teeth (1st incisor, 2nd incisor, & canine) of right & left side of upper & lower jaws and their possible mechanism, & relatively long term disappearance of pain & cancer parameters by one optimal dose of DHEA, Astragalus, Boswellia Serrata, Acupunct Electrother Res. 2009;34(3-4):175–203. Y, Horiuchi N, Jones MK, Lu DP, Shimotsuura Y, Duvvi H, et al

Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus.Tohda C et al. Nov 2006.

Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic. Ping Liu et al. Dec 2017

How does one 'turn on' their Klotho Gene?
This can be accomplished by taking substances proven to activate the Klotho Gene. These substances include the following -

KLOTHO Activators

Ursolic acid and Klotho
Ursolic acid. This substance has been shown to enhance Klotho (Ursolic acid regulates aging process through enhancing of metabolic sensor proteins level. Bahrami SA and Bakhtiari N. Aug 2016) as well as enhance the SIRT 1 Gene, a major gene related to anti-aging (Ursolic Acid Mediates Hepatic Protection through Enhancing of anti-aging Biomarkers. Gharibi S et al. May 2017). Another study found that Ursolic acid was able to regenerate injured nerve myelin sheaths, which are a component of the human nervous system (Ursolic acid induces neural regeneration after sciatic nerve injury. Biao Liu et al. Sept 2013). The neuro-cognitive enhancing herb Berberine also enhances the repair of myelin sheaths (Berberine Promotes Axonal Regeneration in Injured Nerves of the Peripheral Nervous System. Ah Mi Han, et al. April 2012).  And so does lithium (Lithium enhances remyelination of peripheral nerves. Joelle Makoukji, et al. Feb 2012).

Ursolic acid has also been shown to protect the kidneys (Nephroprotective Effect of Ursolic Acid in a Murine Model of Gentamicin-Induced Renal Damage. Preethi G. Pai et al. 2012)

Prunella vulgaris.  Prunella vulgaris  contains ursolic acid  (Ursolic acid enhances pentobarbital-induced sleeping behaviors via GABAergic neurotransmission in mice. Se Jin Jeon et al. June 2015) and has been found to induce deep sleep. Speaking from personal experience I have found that by stimulating the koltho gene through natural foods that I sleep much more better and that my nervous system seems much calmer. The effects being very similar to taking an extract of rhodioa rosea which also “resets” the nervous system. (Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside. Rhodiola rosea L. extract in mice. Perfumi M and  Mattioli L. Jan 2007).

What is also interesting is klotho protects the brain's dopamineric neurons against damage (Klotho Protects Dopaminergic Neuron Oxidant-Induced Degeneration by Modulating ASK1 and p38 MAPK Signaling Pathways . Reynolds K. Brobey, et al. Oct 2015) and dopamine enhances sleep (The involvement of dopamine in the modulation of sleep and waking. Monti JM and Monti D. April 2007).

Previous studies have demonstrated that worms experience a decline in dopamine and serotonin levels with age.

Quote from the study 'Here we report that serotonin (5-HT) and dopamine (DA) level decrease with age in C. elegans.'

Reference
Longevity manipulations differentially affect serotonin/dopamine level and behavioral deterioration in aging Caenorhabditis elegans. Yin JA et al. March 2014. Hence, it is no surprise why herbs that enhance dopamine levels such as Mucuna pruriens (Velvet bean)
(Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Digvijay G. Rana and Varsha J. Galani. March 2014) have been shown to significantly extended  the lifespan in longevity studies conducted on fruit flies (Mucuna pruriens (Velvet bean) Rescues Motor, Olfactory, Mitochondrial and Synaptic Impairment in PINK1B9 Drosophila melanogaster Genetic Model of Parkinsons. Simone Poddighe et al. October 2014).


Dopamine Reduces Oxidative Stress
Oxidative stress is one of the main mechanisms that contributes to aging. It is also interesting to note here that a large scale study that looked at 33 compounds that increased oxidative stress resistance in C. elegans that contained lifespan-extending compounds. The compounds that increased their resistance to stress were three compounds that targeted dopamine receptors with 80 to 83% of animals showing greatly extended lives (A pharmacological network for lifespan extension in Caenorhabditis elegans. Xiaolan Ye, et al. Nov 2013).

Cortisol Levels and Aging
It is a fact that as one ages, changes in their cortisol levels occur (Increased cortisol levels in aging and Alzheimer's disease in postmortem cerebrospinal fluid. Swaab DF et al. Dec 1994). Hence, ursolic acid restores the body's cortisol levels. Evidence for this is found in the published paper titled Tulsi - Ocimum sanctum: A herb for all reasons, published by Marc Maurice Cohen in Dec 2014, which stated that Tulsi - Ocimum sanctum (which is also known as basil) restored cortisol levels. Another study (Holy basil (Ocimum sanctum Linn.) leaf extract enhances specific cognitive parameters in healthy adult volunteers: A placebo controlled study. Sampath S, et al. Jan 2015) also came to the same conclusion and also found that basil enhanced cognition in humans. It is also interesting to note that a combination of rosemary and basil are powerful antibacterials (The potential of use basil and rosemary essential oils as effective antibacterial agents Sienkiewicz M et al. Aug 2013).


Also additional studies have found that flavonoids (luteolin), monoterpenes (linalool), triterpenoids (oleanolic acid and ursolic acid)  have the strongest antileukemic activity (Antileukemic Activity of Selected Natural Products in Taiwan. Lien-Chai Chiang et al. Feb 2003).

Further Reading
Short-term study on the effects of rosemary on cognitive function in an elderly population. Pengelly A et al. Jan 2012.

 

Where is Ursolic Acid Found?

 

Ursolic Acid is widely found in the peels of fruits and in the spices oregano, thyme, rosemary, lavender and thyme (Recent studies on ursolic acid and its biological and pharmacological activity Sook Young Lee et al. March 2016).

Lemon Balm contains ursolic acid (Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity. Awad R et al. Aug 2009). Lemon balm has also been shown to improve memory and boost cognitive performance (Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties.Kennedy DO et al. Oct 2003).

Additional foods that contain ursolic acid include marjoram (Origanummajorana) leaves, sage (Salvia officinalis) leaves, lavender leaves and flowers, eucalyptus (Eucalyptus) leaves and bark, apple (Malusdomestica), black elderberry  (Sambucusnigra) leaves and bark, hawthorn (Crataegus spp.) leaves and flowers, coffee (Coffeaarabica) leaves and the wax layer of many edible fruits (Ursolic Acid—A PentacyclicTriterpenoid with a Wide Spectrum of Pharmacological Activities. Lukasz Wozniak et al. Sept 2015). It is also interesting to note that wax has hydrophobic properties, which we shall cover in greater detail later on as to why it extends the lifespan of lotus seeds.

Also ursolic acid is found in high levels in elderberries (Triterpenoid Acids as Important Antiproliferative Constituents of European Elderberry Fruits. Glensk M et al. June 2017). Ursolic acid is also being explored as a major treatment for suppressed bone density loss that causes osteoporosis (Ursolic Acid--A PentacyclicTriterpenoid with a Wide Spectrum of Pharmacological Activities. Wozniak L et al. Nov 2015).

 

 

Ursolic Acid Synergy
Hyaluronic acid may synergize with Ursolic Acid. I have written an earlier article on how how Hyaluronic acid is a significant anti-aging substance. 

 

 

Resveratrol  and Ursoilc acid work together for healthy skin (Effect of Combined Treatment with Ursolic Acid and Resveratrol on Skin Tumor Promotion by 12-O-tetradecanoylphorbol-13-acetate. Jiyoon Cho et al. June 2015).

Melatonin
Quote from the study – “Melatonin has also shown synergistic effect with other anticancer agents on colorectal tumor. Combination of ursolic acid and melatonin led to an enhanced antiproliferative and pro-apoptotic activities in colon cancer cell lines SW480 and LoVo.” (Melatonin potentiates the antiproliferative and pro-apoptotic effects of ursolic acid in colon cancer cells by modulating multiple signaling pathways. Jingshu Wang et al. Dec 2012).

 
Foods that contain an abundance of melatonin include: Human Breast Milk,  cow's milk, red rice (extremely high in anthocyanins), wheat, oatmeal, cranberries, tomatoes,Basidiomycota mushrooms (extremely high levels of melatonin), Lupin Seeds, Fennel Seeds, Goji Berries, Lentils (very high levels of melatonin), Lupin Seeds, Fennel Seeds, Goji Berries, Lentils (very high levels of melatonin), kidney beans, Pistachio (very high levels of melatonin), wine, green beans, St John’s Wort flowers (very high levels of melatonin) and mulberry leaves (Morus spp. cv. Buriram 60). Herbs with an abundance of melatonin include: Black pepper, Yinyanghuo (Epimediumbrevicornum Maxim), Sangbaipi (Mori Albae, Cortex), Huangbo (PhellodendronamurenseRupr), Sangye (Morus alba L. Leaf), Feverfew leaves, Shiya tea-leaf( Babreumcoscluea), Diding (Viola philipica Cav.), Gouteng (Uncariarhynchophylla), Chantui( Periostracum cicadae), with the highest amounts in Huang-qin (Scutellariabiacalensis) (Dietary Sources and Bioactivities of Melatonin. Xiao Meng, et al. April 2017).

Melatonin levels in the body decline with age and healthy melatonin levels enhance deep sleep, which in turn restores the body's cortisol levels and enhances the youth hormone HGH (Melatonin stimulates growth hormone secretion through pathways other than the growth hormone-releasing hormone. Valcavi R et al. Aug 1993). Another study found that melatonin acts as a potent free radical scavenger and concluded that extensive studies on the use of melatonin for improving the quality of life in advanced age are warranted (Melatonin, human aging, and age-related diseases. Karasek M. Dec 2004). Studies on mice have already confirmed that melatonin in low doses enhances the lifespan of mice as well as significantly decreased their incidents of tumors (Dose-dependent effect of melatonin on life span and spontaneous tumor incidence in female SHR mice. Anisimov VN et al. April 2003).

Also scientific studies have found that increased levels of superoxide dismutase protect the body's kidneys from free radicals (Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase. G L Baker, R J Corry, and A P Autor. Nov 1985).


Further Reading
Free Radicals in Kidney Disease and Transplantation. Abdulla K Salahudeen. 1999


Melatonin Attenuates Memory Impairment Induced by Klotho Gene Deficiency Via Interactive Signaling Between MT2 Receptor, ERK, and Nrf2-Related Antioxidant Potential. Eun-Joo Shin et al. International Journal of Neuropsychopharmacology, 2015, 1–14.

Effects of curcumin and ursolic acid on the mitochondrial coupling efficiency and hydrogen peroxide emission of intact skeletal myoblasts.Tueller DJ et al. Oct 2017.

 

 

 

Ursolic acid exhibits weak “stickiness” properties (Effect of asiatic and ursolic acids on morphology, hydrophobicity, and adhesion of UPECs to uroepithelial cells. Dorota W et al. May 2013) for bad bacteria, much like cranberries (Cranberry proanthocyanidins have anti-biofilm properties against Pseudomonas aeruginosa. Robert K Ulrey et al. Dec 20140.  This term is known as hydrophobic and it is what lotus seeds are naturally coated with allowing them to sprout after 1,300 years (Long-living lotus: germination and soil {gamma}-irradiation of centuries-old fruits, and cultivation, growth, and phenotypic abnormalities of offspring.Shen-Miller J et al. Feb 2002),

(Ursolic acid, an antagonist for transforming growth factor (TGF)-ß1 Edited by Veli-PekkaLehto Author links open overlay panel. Shigeru Murakami et al. May 2004), (Potential Protective Effects of Ursolic Acid against Gamma Irradiation-Induced Damage Are Mediated through the Modulation of Diverse Inflammatory Mediators. Hong Wang et al. June 2017).

Further Reading

The Herb Cordyceps
This unique herb has been shown to enhance / stimulate the Klotho Gene (Effect of Cordyceps sinensis extract on Klotho expression and apoptosis in renal tubular epithelial cells induced by angiotensin II. Tang R, Zhou Q, Shu J, et al. Journal of Central South University. 2009;34(4):300–307). Speaking from personal experience, I have had great results taking cordyceps with Spanish Moss extract at the ratio of 2:1 and up to 10:1.  You can learn more about Spanish Moss in my article titled Yttrium extends Lifespan (www.ez3dbiz.com). Hence it would make sense that Cordyceps benefits the kidneys, because as we discussed earlier, Klotho's main influence on the body is via the kidneys. A study found that Cordyceps has been found to be of benefit for people with chronic kidney disease (Cordycepssinensis (a traditional Chinese medicine) for treating chronic kidney disease. Zhang HW et al. Dec 2014). Also the herb astragalus is also used to treat chronic kidney disease (Astragalus (a traditional Chinese medicine) for treating chronic kidney disease. H.W. Zhang et al. October 22, 2014).

 

Resveratrol
(Resveratrol increases anti-aging Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway. S.C. Hsu et al. Aug 2014).

 

Vitamin D
(FGF23, klotho and vitamin D interactions: What have we learned from in vivo mouse genetics studies? Razzaque M. 2012). It is interesting to note that when vitamin D is combined with curcumin, it enhances its effects (Anticancer Efficacy of Polyphenols and Their Combinations. Aleksandra Niedzwiecki. et al. Sept 2016).

 

 

Magnesium
(Magnesium modulates parathyroid hormone secretion and upregulates parathyroid receptor expression at moderately low calcium concentration. Rodríguez-Ortiz ME et al. Feb 2014).

Valsartan
Valsartan is a non-prescription pharmaceutical. (The Effects of Valsartan on Renal Klotho Expression and Oxidative Stress in Alleviation of Cyclosporine Nephrotoxicity. Raeisi S. et al. June 2017).

N-acetylcysteine
(Influence of N-acetylcysteine on Klotho expression and its signaling pathway in experimental model of chronic cyclosporine nephropathy in mice. Piao SG et al. July 2013).

Vitamin E
(Klotho sensitive regulation of dendritic cell functions by vitamin E. Nguyen ThiXuan et al. Nov 2016). Please note, vitamin E has not been found to be a significant lifespan extender in many studies and excess amounts are detrimental (Vitamin E may affect the life expectancy of men, depending on dietary vitamin C intake and smoking. Hemilä H and Kaprio J. March 2011).  It is best use short term.

 

Sulodexide
(Sulodexide Protects Renal Tubular Epithelial Cells from Oxidative Stress-Induced Injury via Upregulating Klotho Expression at an Early Stage of Diabetic Kidney Disease. Yu Ning Liu, et al. Aug 2017). Sulodexideexists is  a sulfated polysaccharide that comes from the intestine of pigs.  It is interesting to note that a substance made from pig intestines called “pixie dust” has shown promise in regenerating human body parts (Patients regrow muscles with pig bladder tissue. CBS news).

ACE inhibitors
(Effects of Klotho on fibrosis and cancer: A renal focus on mechanisms and therapeutic strategies? Author links open overlay panel. RikMencke  et al. Nov 2017). Pomegranate is one of the best ACE inhibitors (Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Aviram M et al. Sept 2001).

 

 

 

Fosinopril (by prescription only)
(Role of Fosinopril and Valsartan on Klotho Gene Expression Induced by Angiotensin II in Rat Renal Tubular Epithelial Cells. Q. Zhou et al. June 2010).

 

 

AT1 receptor antagonists
(Effects of Klotho on fibrosis and cancer: A renal focus on mechanisms and therapeutic strategies? Author links open overlay panel. Rik Mencke et al. Nov 2017).

EGCG. Found in abundance in green tea
(Epigallocatechin-3-O-(3-O-methyl)-gallate-induced Differentiation of Human Keratinocytes Involves Klotho-Mediated Regulation of Protein Kinase-cAMP Responsive Element-Binding Protein Signaling Hyoung-June Kim et al. Apr 2014).

Quote from study “A combination of green tea polyphenols, a dietary DNA methyltransferase inhibitor and sulforaphane, a dietary histone deacetylase inhibitor leads to the epigenetic reactivation of silenced tumour suppressor genes such as p21 CIP/WAF1 and KLOTHO” (Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies. Anna Maria Mileo and Stefania Miccade). Note - excess consumption of green tea has been found to increase one's risk of liver cancer  (Green tea and liver cancer. Francesca Bravi et al. April 2017). Hence it is best used in moderation.

Sulforaphane with Green Tea
Quote from another study “These results suggest that the reactivation of KLOTHO by the combinations of GTPs (green tea polyphenols)  and SFN (sulforaphane) leads to the inhibition of IGF-1 and its downstream cascade in human breast cancer cells.” (Epigenetic reactivation of p21CIP1/WAF1 and KLOTHO by a combination of bioactive dietary supplements is partially ERa-dependent in ERa-negative human breast cancer cells. Sonam Sinha et al. Feb 2015). Sulforaphane is found in high levels in broccoli and brusels sprouts. It is also interesting to note that radishes contain sulforaphane. We shall cover radishes in more detail later on.

Factors that Limit Klotho Expression

If you want to avoid the Klotho gene from being supressed, avoid the following: Excess Phosphate (Phosphate and Klotho Makoto Kuro-o. Feb 2011). Phosphate is found in high levels in dairy.

Excess Iron. (Iron chelation and a free radical scavenger suppress angiotensin II-induced downregulation of klotho, an anti-aging gene, in rat. Saito K et al. Sept 2008). Found in high levels in spinach.  Foods high in both iron and phosphate include: Thyme, Basil, Spearmint, Marjoram, Seaweed, Turmeric, Parsley, Dill and celery seed (https://ndb.nal.usda.gov). Hence, it may be a good idea to take an Iron chelator with basil or thyme, as these two herbs contain ursolic acid which enhances the Klotho gene due to their ursolic acid content. Turmeric is one natural iron chelator. Other iron chelators include magnesium and calcium chelate phosphate. Lanthanum also chelates iron and I have written in my Spanish Moss article titled: Do Metals that affect time slow the aging process? that Spanish Moss, contains Lanthanum.  

Anthocyanins and Klotho
In my book Foods, Pharmaceuticals extend lifespan, I show that anthocyanins are one of the most powerful substances shown to extend lifespan (Cranberry anthocyanin extract prolongs lifespan of fruit flies. Wang L et al. Sept 2015). One of the foods that contain extremely above average amounts of anthocyanins is the chokeberry (Anthocyanins from Black Chokeberry (Aroniamelanocarpa Elliot) Delayed Aging-Related Degenerative Changes of Brain. Wei J et al. July 2017). Chokeberry also contains extremely high amounts of polyphenols (Effects of polyphenol-rich chokeberry juice on antioxidant/pro-oxidant status in healthy subjects. Kardum N et al. August 2014). A research study found that the anthocyanins in chokeberry enhanced the Klotho gene (Anthocyanins from Black Chokeberry (Aroniamelanocarpa Elliot) Delayed Aging-Related Degenerative Changes of Brain. Wei J et al. July 2017) and resveratrol happens to be a natural polyphenol (Resveratrol increases Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway. Hsu SC et al. August 2014).

Summary
Polyphenol rich foods such as black chokeberry may stimulate Klotho gene expression. Two other foods high in anthocyanins include Elderberries and Mulberries.  Further research is needed to see if these enhance the activity of the klotho gene. 

Klotho as a Potent Diabetes Fighter
Levels of circulating Klotho have been found to be at low levels in people who have diabetes (Decreased Circulating Klotho Levels in Patients Undergoing Dialysis and Relationship to Oxidative Stress and Inflammation. Hyung Jung Oh et al. Feb 2015) and a depressed Klotho gene also contributes to increased inflammation in people with diabetes (Klotho Depletion Contributes to Increased Inflammation in Kidney of the db/db Mouse Model of Diabetes via RelA (Serine)536 Phosphorylation. Yanhua Zhao et al. July 2011).

Klotho, Kidneys and Radishes
Other clinical studies have shown that persons suffering from chronic kidney disease have a Klotho deficiency (Klotho and Chronic Kidney Disease. Ming Chang Hu et al. May 2013).  As we covered earlier on, in anti-aging Tao Medicine, the kidneys represent "Jing" which stores the life force and radishes are a good food that is important for healthy kidneys. Healthly amounts of "Jing" contribute to a long life. Because one of the primary regions of the body that enhances Klotho activity comes from the kidneys, it makes sense that radishes are good food to support healthy kidney functioning and may stimulate the Klotho gene, although no studies have yet been conducted to confirm this hypothesis.

 

Radishes dissolve Kidney Stones
Calcium oxalate stones are a kidney stone that contribute to the condition known as calcium oxalate excretion, which comes from excess levels of calcium. A study found that a 2 week diet including radishes dissolved calcium oxalate (Influence of radish consumption on urinary calcium oxalate excretion. Kumar A. June 2004). What is also interesting is that the herb horsetail, which contains ursolic acid (Effect of Ethanol Root Extract of Equisetum arvense (L) on Urinary Bladder Activity in Rats and Analysis of Principal Plant Constituents. Haiying Zhang et al. June 2015), is also used for kidney health and well being (Horsetail plant (not only) for the kidney. Feb 2005) as well as for the healing of topical wounds (The Effect of Equisetum Arvense (Horse Tail) Ointment on Wound Healing and Pain Intensity After Episiotomy: A Randomized Placebo-Controlled Trial. Azam Asgharikhatooni et al. March 2015). Also it is interesting to note that radishes contain abundant amounts of potassium (https://ndb.nal.usda.gov) and Klotho plays a key role in the regulation of the calcium and potassium ion channels (Chapter Three - Klotho-Dependent Cellular Transport Regulation. Author links open overlay panel. M. Sopjani, M. Dërmaku-Sopjani). Another interesting fact is fennel seeds contain an abundance of calcium and potassium. Fennel seeds are used in the anti-aging extract known as the St. Germain Formula, which I go into more detail in my anti-aging books. The St. Germain formula is reputed to have been created by the alchemist St. Germain and I have also written an extensive article about the St. Germain Formula titled: The Longevity Formula of Count Saint Germain.  

One of the interesting things I had always found when researching Alchemy, is that just a few grains of the red powder, when added to wine, were supposed to restore one to health and a long life.  I had read accounts of where a person took too much red powder mixed with wine and died.  Could it be that one of the secrets of the alchemists was the red power reacting with the red wine that caused the profound healing and longevity to occur?  It is a well known fact that red wine extends lifespan (Longevity nutrients resveratrol, wines and grapes, Istvan Lekli, Diptarka Ray, and Dipak K. Das. Sept 2009). Hence the red powder may be acting as a catalyst of some sort.  Red wine has been shown to be good for the kidneys (Effects of red wine consumption on kidney FA composition. Araya J. March 2003).