Remove Your Senescent Cells with Fisetin

Fisetin is a naturally occurring flavonoid found most abundantly in strawberries.

The ability of the natural flavonoid fisetin to remove toxic senescent zombie cells is a major development in age reversal science…let’s take a look at the research…

Fisetin is a Natural Senolytic

Senolytics are pharmaceuticals or nutraceuticals with unique abilities to remove dangerous senescent zombie cells.

Senescent Zombie Cells and Fisten

The researchers at the Scripps Institute compared fisetin against other powerful natural compounds, including resveratrol, luteolin, rutin, EGCG from green tea, curcumin, myricetin, apigenin, among others. This study revealed fisetin to be far and away the most effective of these compounds in removing toxic senescent cells.

In old mice, fisetin reduced senescence markers in multiple tissues (also in human tissue). Feeding fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related disease and extended lifespan.

These two mice are litter mates; the only difference is that the mouse on the left has aged normally while the mouse on the right has had its senescent cells removed and appears considerably more healthy.

University of Minnesota Medical School faculty members Dr. Paul D. Robbins and Dr. Laura J. Niedernhofer, along with Mayo Clinic investigators Dr. James L. Kirkland and Dr. Tamara Tchkonia published a breakthrough study…

“Fisetin is a senotherapeutic that extends health and lifespan” in the journal EBioMedicinehttps://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext

During their study, they discovered fisetin was able to remove senescent cells from aged mice, which improved their health and lifespan.

The researchers found that getting rid of only 30% of senescent cells is enough to have a major impact on health and longevity.

Dr. Niedernhofer states, “Senescent cells aren’t like cancer where to cure it, you have to kill every cancer cell. Fisetin, the natural flavonoid, removed 25 to 50% of senescent cells depending on the organ. These mice fed fisetin late in life (the equivalent of 75 years in humans) lived 10-15% longer than the mice that didn’t get the fisetin. This represents a 50% increase in their remaining lifespan.”

The researchers continued, “This fisetin is a natural compound present in small amounts of many fruits and vegetables. Importantly, no adverse effects of fisetin have been reported, even when given at high doses.”

“Thus, our results suggest that supplementation or even intermittent treatment with this safe natural product could improve healthy aging, even in elderly individuals.”

The researchers of this study have confirmed that fisetin is targeting and destroying senescent cells rather than simply blocking their signals or altering them in some beneficial way but not removing them.

“Nutraceuticals can be used to mimic the anti‐aging effects of longevity drugs without adverse effects.”
~ Alex Zhavoronkov, Ph.D. / Editor, Cell Aging
credit: Salk Institute of Biological Studies

A daily dose of the antioxidant FISETIN keeps mice—even those with genetic mutations linked to Alzheimer’s—from experiencing memory and learning deficits as they age.

“We had already shown that in normal animals, fisetin can improve memory,” says Pamela Maher, Ph.D, a senior staff scientist in Salk’s Cellular Neurobiology Laboratory, who led the new study. “What we showed here is that it also can have an effect on animals prone to Alzheimer’s.

More than a decade ago, Maher discovered that fisetin helps protect neurons in the brain from the effects of aging. She and her colleagues have since—in both isolated cell cultures and mouse studies—probed how the compound has both antioxidant and anti-inflammatory effects on cells in the brain.

Most recently, they found that fisetin turns on a cellular pathway known to be involved in memory.

So Maher—who works with Dave Schubert, Ph.D., the head of the Cellular Neurobiology Lab—turned to a strain of mice that have mutations in two genes linked to Alzheimer’s disease. The researchers took a subset of these mice and, when they were only three months old, began adding fisetin to their food.

As the mice aged, the researchers tested their memory and learning skills with water mazes. By nine months of age, mice that hadn’t received fisetin began performing more poorly in the mazes. Mice that had gotten a daily dose of fisetin however, performed as well as normal mice, at both nine months and a year old.

“Even as the disease would have been progressing, the fisetin was able to continue preventing symptoms,” Maher says.

Pamela Maher – Salk Institute for Biological Studies, USA. Pamela obtained her Ph.D. in Biochemistry from the University of British Columbia – She has over 100 publications in peer-reviewed journals. Her research is currently funded by NIH.

In collaboration with scientists at the University of California, San Diego, Maher’s team next tested the levels of different molecules in the brains of mice that had received doses of fisetin and those that hadn’t.

In mice with Alzheimer’s symptoms, they found pathways involved in cellular inflammation were turned on. In the animals that had taken fisetin, those pathways were dampened and anti-inflammatory molecules were present instead.

Clearing out the brain’s “zombie cells” offers new approach against dementia

“Senescent cells are known to accumulate with advancing natural age and at sites related to diseases of aging, including osteoarthritis; atherosclerosis; and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s,” says Darren Baker, Ph.D., a Mayo Clinic molecular biologist.

“Zombie cells, aka senescent cells, have been found to accumulate in the brain ahead of the toxic protein build-ups that are generally implicated in Alzheimer’s disease and dementia.”

“In prior studies, we have found that elimination of senescent cells from naturally aged mice extends their healthy life span.”

In his research, the team used a model that imitates aspects of Alzheimer’s disease.

“When senescent cells were removed, we found that the diseased animals retained the ability to form memories, eliminated signs of inflammation, did not develop neurofibrillary tangles, and had maintained normal brain mass.”

Darren Baker, Ph.D. and Tyler Bussian Ph.D. Candidate Mayo Clinic

Fisetin and Beta Amyloid Protein

Alzheimer’s disease is a devastating and progressive neurodegenerative disease and is characterized pathologically by the accumulation of amyloid beta (Aβ) and of tau proteins in the brain, which lead to cognitive disorders.

Research published in Molecular Neurobiology (2017) reports that fisetin has a potent neuroprotective effect against Aβ1–42-induced neurotoxicity:

https://www.ncbi.nlm.nih.gov/pubmed/26944285

“These results demonstrate that polyphenolic flavonoids such as fisetin could be a beneficial, effective and safe neuroprotective agent for preventing neurological disorders such as Alzheimer’s Disease.

Further studies in support of Fisetin

One of the common mechanisms by which fisetin appears to work is via the reduction of inflammation, which could either be via removing senescent cells and their inflammatory secretions or by mediating immune response and blocking inappropriate inflammatory signaling.

While not all of these studies directly relate to aging, many are linked to inflammation, which is critical to aging, so the data could be valuable in this respect.

There have been other studies, which found that fisetin has a potent effect on inflammation via blocking the activity of lipoxygenases, thus reducing the level of pro-inflammatory cytokines.

Fisetin also appears to have a potential application in combating high blood sugar in diabetics, which can cause inflammation of blood vessels and tissue damage. Researchers found that fisetin was able to block this inflammatory response in human cell lines and in mice.

“Based on our ongoing work, we think Fisetin might be helpful as a preventative for many age-associated neurodegenerative diseases, not just Alzheimer’s, and we’d like to encourage more rigorous study of it.”
~ Pamela Maher, Ph.D / Salk Institute for Biological Studies

The Cognitive Benefits of Fisetin:

• Encourages New Brain Growth
• Improves Memory
• Protects Against Brain Degeneration
• Decreases Brain Damage After Stroke
• Minimizes Brain Damage From Injury
• Neuroprotective
• May Treat Depression
• Increases Levels of Glutathione
• Crosses the Blood Brain Barrier

Fisetin also:

• Has Anti-Inflammatory Properties
• May Prevent and Treat Cancer
• A Protector of Men’s Prostates
• Improves Blood Flow
• Lowers Blood Pressure
• May Help Treat Diabetes
• Helps with Blood Sugar Issues
• Reduces Glycation
• May Extend Lifespan

MORE great benefits of Fisetin…

• Activates the Longevity Gene: SIRT 1
• May Lower Body Weight
• Protects Bone
• Protects Skin From Sun Damage

• Helps Maintain Energy Levels
• Works to Lower Body Weight
• It May Be a Great Pain Reliever
• Boosts Energy Levels

Senescent Zombie Cells are directly linked to your most serious age related health challenges:

  • Body Wide Inflamm-aging
  • Cellular Dysfunction and Mutations
  • Heart & Vascular Degeneration
  • Deteriorating Brain Function
  • Memory Loss
  • Poor Blood Sugar Health
  • Worsening Insulin Resistance
  • Breakdown of Joint Cartilage
  • Loss of Lung & Kidney Function
  • Vision Abnormalities

For years, and even decades, you’ve been building up contaminating levels of destructive senescent zombie cells…

Finally…and for the first time…you can start removing these insidious cells…and remove them FAST!!!

Here’s a Special VIP Offer for Zombie Cell Detox which Contains 100mg of Pharmaceutical Grade FISETIN in Each 1 Capsule Serving:

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Be among the first lucky people to experience the benefits of the most advanced age reversal science…

Take advantage of this introductory offer for Zombie Cell Detox, the first science-based supplement to remove poisonous senescent zombie cells before they seriously compromise your vital organs and systems.

The ingredient in Zombie Cell Detox has been researched at the Mayo Clinic on Aging and the Scripps Institute and it removes 25 to 50% of toxic senescent cells…plus these very old laboratory animals (75 in human years) lived 10-15% longer…this represents a 50% increase in their remaining lifespan.

So start protecting your body against the most dangerous health threatening cells with Zombie Cell Detox…100% Money Back Guaranteed!

About The Authors:

Rob Martin has been at the forefront of the nutraceutical / life extension movement for nearly 40 years.

Through radio, television, publishing and video, he has reached millions with his science-based message for achieving optimal health and longevity. In the area of product development, Rob has created scores of cutting edge nutraceutical formulations for medical practices, natural pharmacies, and national nutritional supplement companies.

This includes Ageless Male, one of the most successful product launches ever in the nutraceutical industry, igniting a sea of major copycat natural testosterone boosters.

His most recent product innovations are TeloVite, the first cellular longevity multivitamin…and Zombie Cell Detox, the first evidence-based natural formulation to target senescent “zombie cells.”

For over 20 uninterrupted years, right up to this day, Rob has been a national radio spokesman for leading nutraceutical & cosmeceutical companies, integrative medical centers and natural pharmacies…he has made countless appearances on over 150 radio shows coast-to-coast…and hosted Health Radio News, on SiriusXM in 2012 &13.

Starting in February 2019, Rob is producing and hosting Living Beyond 100, a radio show devoted to reporting on evidence-based advances from the frontier of longevity science. For more information about Rob Martin, please visit: http://robmartinmedia.com

Graham Simpson, M.D. Is Living Beyond 100 Chief Medical Officer and is the Founder & Medical Director of the innovative Intelligent Health Center, Dubai, UAE.

Dr. Simpson graduated from the University of Witwatersrand Medical School in Johannesburg, South Africa and is Board Certified in Internal Medicine, Emergency Medicine, and Age Management Medicine (A4M). He is a founding member of the American Holistic Medical Association (AHMA) and is a licensed homeopath. Dr. Simpson has also taught as an assistant professor of medicine at the University of Nevada, Reno.

He is the author of WellMan (Live Longer by Controlling Inflammation); co-author of Spa Medicine with Dr. Stephen Sinatra; and the forthcoming Reversing CardioMetabolic Disease.

Dr. Simpson was the Founder of PrimalMD; the Founder of the Eternity Medicine Institute; Paleo4me; and the Inflamaging Physician Network. He is a Consultant to Cenegenics, Inc

He has practiced I.N.T.E.G.R.A.L. Health for many years and remains committed to delivering Proactive Health to physicians and clients around the world.

SCIENTIFIC LITERATURE:

SENESCENT CELL REFERENCES

James Kirkland, T. Tchkonia, Y. Zhu, L. Niedernhofer, and D. Robbins. The Clinical Potential of Senolytic Drugs. (2017). Journal of the American Geriatrics Society. DOI: 10.1111/jgs.14969. Available Online.

Carlos López-Otín, M. A. Blasco, L. Partridge, M. Serrano, and G. Kroemer.The Hallmarks of Aging. (2013). Cell, 153(6), 1194-1217. Available Online.

Jan M. van Deursen. The role of senescent cells in ageing. Nature. May 22, 2014; 509(7501): 439–446. Available Online.

Jeon, O. H., Kim, C., Laberge, R. M., Demaria, M., Rathod, S., Vasserot, A. P., … & Baker, D. J. (2017). Local clearance of senescent cells attenuates the development of post-traumatic osteoarthritis and creates a pro-regenerative environment. Nature medicine, 23(6), 775-781.

Xu, M., Bradley, E. W., Weivoda, M. M., Hwang, S. M., Pirtskhalava, T., Decklever, T., … & Lowe, V. (2016). Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, glw154.

Childs, B. G., Baker, D. J., Wijshake, T., Conover, C. A., Campisi, J., & van Deursen, J. M. (2016). Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science, 354(6311), 472-477.

Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010). The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression. Annual Review of Pathology, 5, 99–118

Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., Van De Sluis, B., … & van Deursen, J. M. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479(7372), 232-236.

Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’Hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658

Roos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., … & Zhu, Y. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell.

Yousefzadeh, M. J., Zhu, Y., McGowan, S. J., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., … & McGuckian, C. (2018). Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine, 36, 18-28.

Ahmad A1, Ali T1, Park HY2, Badshah H1, Rehman SU1, Kim MO3.Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … & O’Hara, S. P. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging cell, 14(4), 644-658

FISETIN REFERENCES

Mayo Clinic on Aging Fisetin Study:
https://www.ebiomedicine.com/article/S2352-3964(18)30373-6/fulltext

Maher, Pamela / Fisetin / Salk Institute Studies:

(2006)

Maher P, Akaishi T, Abe K (2006) Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory. Proceedings of the National Academy of Sciences of the United States of America 103, 16568-16573.

(2014)

https://www.salk.edu/news-release/natural-plant-compound-prevents-alzheimers-disease-in-mice/

Currais A, Prior M, Dargusch R et al. (2014) Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer’s disease transgenic mice. Aging cell 13, 379-390
(2015)

Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function: http://onlinelibrary.wiley.com/doi/10.1111/acel.12185/full

(2017)

https://www.salk.edu/news-release/evidence-shows-natural-plant-compound-may-reduce-mental-effects-aging/

Additional Fisten Studies:

Kim H, Park BS, Lee KG et al. (2005) Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. Journal of agricultural and food chemistry 53, 8537-8541.

Ushikubo H, Watanabe S, Tanimoto Y et al. (2012) 3,3′,4′,5,5′-Pentahydroxyflavone is a potent inhibitor of amyloid beta fibril formation. Neuroscience letters 513, 51-56.

Kim S, Choi KJ, Cho SJ et al. (2016) Fisetin stimulates autophagic degradation of phosphorylated tau via the activation of TFEB and Nrf2 transcription factors. Sci Rep 6, 24933.

Chuang JY, Chang PC, Shen YC et al. (2014) Regulatory effects of fisetin on microglial activation. Molecules 19, 8820-8839.

Cho N, Lee KY, Huh J et al. (2013) Cognitive-enhancing effects of Rhus verniciflua bark extract and its active flavonoids with neuroprotective and anti-inflammatory activities. Food Chem Toxicol 58, 355-361.

Ahmad A, Ali T, Park HY et al. (2016) Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice. Mol Neurobiol.

Lopez-Lazaro M, Willmore E, Austin CA (2010) The dietary flavonoids myricetin and fisetin act as dual inhibitors of DNA topoisomerases I and II in cells. Mutat Res696, 41-47.

Lim DY, Park JH (2009) Induction of p53 contributes to apoptosis of HCT-116 human colon cancer cells induced by the dietary compound fisetin. Am J Physiol Gastrointest Liver Physiol 296, G1060-1068.

Bothiraja C, Yojana BD, Pawar AP et al. (2014) Fisetin-loaded nanocochleates: formulation, characterisation, in vitro anticancer testing, bioavailability and biodistribution study. Expert opinion on drug delivery 11, 17-29.

Strick R, Strissel PL, Borgers S et al. (2000) Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proceedings of the National Academy of Sciences of the United States of America 97, 4790-4795.

Vaqar M. Adhami, Rahul K. Lall and Hasan Mukhtar DOI: 10.1158/1538-7445.AM2012-612 Published April 2012Abstract 612: Fisetin, a dietary flavonoid and novel mTOR
inhibitor for treatment and prevention of prostate cancer

Ahmad A(1), Ali T(1), Park HY(2), Badshah H(1), Rehman SU(1), Kim MO(3). Neuroprotective Effect of Fisetin Against Amyloid-Beta-Induced Cognitive/Synaptic Dysfunction, Neuroinflammation, and Neurodegeneration in Adult Mice.

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