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JAMA (Journal of the American Medical Association):
"Senolytic Drugs could transform care of older adults with multiple chronic diseases."


Senolytic Drugs Selectively Target and destroy Senescent Cells


"seno" re: senescent cells, lytics re: destruction
"The Technology to stop or slow down the aging process EXISTS...
But it ain't gonna do you any good unless you apply it to your body!" - Ellis Toussier

I bumped into a new anti-aging therapy, and I want to bring it to your attention because the Mayo Clinic and the Journal of the American Medical Association (JAMA) and Life Extension Foundation and many others whose opinion I respect think that this might change how doctors will treat OLD patients (greater than age 50) in the future.

In a study published in July, 2018 in Nature Medicine, scientists at the Mayo Clinic found that with advancing age "senescent cells" progressively take the human body to disease states ranging from cancer and diabetes to arthritis, loss of vision, dementia, heart disease, kidney disease, etc. etc.

A "senescent cell" is a cell in our body whose telomeres have reached their "Hayflick Limit" ie, its telomere has gotten so short that the cell cannot divide anymore. It is not precisely dead, but it is not a healthy cell anymore. It is a "zombie" cell, and it emits toxic compounds that cause inflammation and damage nearby cells.

It should be eliminated by our immune system, but as we get older and our immune system gets weaker, some of these cells manage to stay in our body.

A Senescent cell secretes pro-inflamatory substances which damage nearby cells. This causes them to also become senescent, which amplifies their effect. As senescent cells accumulate in our body, our walking pace slows down, the incidence of cancer and heart disease increase sharply, kidneys and liver dysfunction increases, osteoarthritis and diabetes increase... in short, all of the disabilities associated with advancing age increase. Senescent cells seem to be a big cause of infirmity in old age.

The scientists at Mayo Clinic used a "Tyrosine kinase inhibitor" to remove senescent cells from the body of mice. Specifically, they used "Sprycel" (dasatinib) which is a miracle drug used for Chronic Myelogenous Leukemia (CML).

They were surprised to see that Sprycel plus "quercetin" (a bio-flavenoid which you can buy at any health food store) extended the lifespan of mice about 35%, and it also improved their quality of life...

They repeated the experiment on very old mice, close to the end of their life. Amazing results: cardiac function and carotid vascular reactivity were improved a mere FIVE DAYS AFTER A SINGLE DOSE of Sprycel (dasatinib) plus quercetin. Symptoms of frailty like tremors, urinary incontinence, and osteoarthritis were reduced, and exercise endurance was greatly increased.

A SINGLE DOSE of dasatinib + quercetin in "old" mice LED TO IMPROVED EXERCISE CAPACITY FOR AT LEAST 7 MONTHS FOLLOWING DRUG TREATMENT!!!


Before and After removal of senescent cells in mice

What is interesting is that, like the mice of the experiment, humans also have senescent cells, and they cause the same age related diseases as they do in mice !

So, now that we know that mice live longer and with better quality of life if we remove their senescent cells, scientists want to know if removing senescent cells from humans will also result in a better quality of life, and perhaps a longer lifespan for humans.

I think it is unlikely that removing senescent cells from humans will extend lifespan 35% as it did in mice. But I think it might extend human lifespan another 10 years, which is not so bad!... And, more importantly, it has the potential to improve the quality of life in those final years!

It seems like a good guess to me that if I can remove senescent cells from my body, this will decrease the chance of me having many of the diseases associated with old age, and I want to be healthy and viable for as long as possible.

So... What to do? I am an Old Man, seventy three years of age. I don't have TIME to wait for the results of the clinical trial now taking place on very sick kidney disease patients.

I have decided that I will get quercetin and either Sprycel or Tasigna, which are both tyrosine kinase inhibitors. And I will try to do the same experiment on me, too. I know that the technology to reverse or stop or slow down the aging process already exists... but it can't do me any good unless I apply it to my body !

And so... I will apply it to my body.

In any case, I don't expect that Sprycel or Tasigna will have very serious side effects because they are used daily for many years by leukemia patients, and most do not have any side effects from them at all... And in any case, I think no side effect will happen in three days.

Ellis Toussier - November, 2018
for comments, please write to me to : etoussier@safe-mail.net

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Mayo Clinic experiment on very old mice: removing senescent cells extended their life and healthspan.

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An experiment on myself, based on the Mayo Clinic Clinical Trial (Senescence in Chronic Kidney Disease) using Tasigna instead of Sprycel.

What I did:

In late November, 2018 I took 2 x Tasigna 200 mgs pills in the morning, 2 Tasigna 200 mgs pills 12 hours later, for three days. This was a total of 12 Tasigna (nilotinib) 200 mgs. Plus I took 2 Quercetin 600 mgs pills for three days, and continued taking them after I stopped taking Tasigna. I ate very healthy and low carb.

Why I did it:

I am an Old Man, seventy three years of age. I don't have TIME to wait for the results of the clinical trial now taking place on very sick kidney disease patients. In any case, I did not expect that Sprycel or Tasigna would have very serious side effects because they are used daily for many years by leukemia patients, and most of them only have good results and they do not have any side effects at all...

And in any case, I expected that no side effect would happen in three days.

Why I used Tasigna instead of Sprycel:

I used Tasigna because I could buy it for much less than Sprycel... Both Sprycel and Tasigna are extremely expensive, and so, I used the least expensive one that I guessed will do the job. I learned that Tasigna has had better results than Sprycel to completely cure patients with chronic leukemia. And since they both work by blocking the signal that causes leukemia cells to divide (see diagram below) I guessed Tasigna would also remove senescent cells, like Sprycel did... perhaps even more, because it has had better results as a medicine for leukemia patients...

How I did it:

necessary: 12 pills Tasigna (nilotinib) 200 mgs + Quercetin 600 mgs...

optional: blood glucose meter and test strips

Diet: Very very low carbohydrate diet for three days... keep blood glucose below 100 mg/dl, preferably around 85 mg/dl or lower.

Take 2 pills of Tasigna 200 mgs every 12 hours for 3 days. Take after fasting at least 2 hours, do not eat for at least one hour after Tasigna

Take 2 pills (1200 mgs) Quercetin every 24 hours

Quercetin can be continued after three days for as long as there are no side effects...

The result:

I did not feel nausea, or headache, my hair did not fall off, no rash, no pain in bones or muscles... no side effect at all, during and after three days (12 pills of 200 mgs) Tasigna.

I do not know if any senescent cells were actually removed from my body. But maybe some (or many) were.

Two weeks after I drank Tasigna and quercetin for three days: I have BETTER BALANCE... I can balance on one foot better than I could, before... and I can BEND DOWN to pick up something from the floor, better than I could, before...

The important thing to me is that perhaps some senescent cells were actually removed from my body... and I had zero side effects. So maybe I win, but surely I didn't lose.

For more information about this one-man experiment, write to me from a Protonmail.com or safe-mail.net account. I will not answer if your e-mail is not encrypted:

etoussier@safe-mail.net
Ellis Toussier

======================

What is the life expectancy of someone with Chronic Myelogenous Leukemia (CML)?

The development of tyrosine kinase inhibitors, imatinib(Glivec)... dasatinib (Sprycel)... and nilotinib (Tasigna)... has dramatically extended the expected life span of patients living with CML. Life expectancy was once only 3-7 years after the diagnosis of CML was determined. Today we measure life expectancy in decades with most individuals living with CML anticipating a normal lifespan.

What is a tyrosine kinase inhibitor? And if tyrosine kinase inhibitors are a miracle drug for CML, why do they also clear out senescent cells?

(imatinib) GLIVEC, (dasatinib) SPRYCEL, and (nilotinib) TASIGNA belong to the signal transduction inhibitor category of targeted therapies. They particularly inhibit multiple protein-tyrosine kinases.

A tyrosine kinase inhibitor is a type of enzyme that adds a phosphate group to a protein. This can turn "on" or "off" an abnormal protein that is found only in leukemia cells, but not in normal cells.

This blocks the action of this abnormal protein, and therefore it blocks the signal that this abnormal protein sends out to cancer cells, telling them to multiply. This helps stop the spread of cancer cells.


diagram shows how a tyrosine kinase inhibitor blocks the signal to duplicate inside the cell

This is also how tyrosine kinase inhibitors affect senescent cells. This results in senescent cell apoptosis (cell suicide) after which they are finally cleared from the body.

The beauty of this is that tyrosine kinase inhibitors only affect senescent cells that have this abnormal protein, but they do not affect or harm healthy cells that do not have the abnormal protein.

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(YouTube) William Falloon talks at RAADFEST 2018, (start video at 18:20 to about 28:00)

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https://www.ncbi.nlm.nih.gov/pubmed/29988130

Abstract

Physical function declines in old age, portending disability, increased health expenditures, and mortality. Cellular senescence, leading to tissue dysfunction, may contribute to these consequences of aging, but whether senescence can directly drive age-related pathology and be therapeutically targeted is still unclear. Here we demonstrate that transplanting relatively small numbers of senescent cells into young mice is sufficient to cause persistent physical dysfunction, as well as to spread cellular senescence to host tissues.

Transplanting even fewer senescent cells had the same effect in older recipients and was accompanied by reduced survival, indicating the potency of senescent cells in shortening health- and lifespan.

The senolytic cocktail, dasatinib plus quercetin, which causes selective elimination of senescent cells, decreased the number of naturally occurring senescent cells and their secretion of frailty-related proinflammatory cytokines in explants of human adipose tissue.

Moreover, intermittent oral administration of senolytics to both senescent cell-transplanted young mice and naturally aged mice alleviated physical dysfunction and increased post-treatment survival by 36% while reducing mortality hazard to 65%.

Our study provides proof-of-concept evidence that senescent cells can cause physical dysfunction and decreased survival even in young mice, while senolytics can enhance remaining health- and lifespan in old mice.

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http://www.latimes.com/science/sciencenow/la-sci-sn-anti-aging-cocktail-20180710-story.html

This drug cocktail reduced signs of age-related diseases and extended life in mice and human cells

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https://clinicaltrials.gov/ct2/show/record/NCT02848131?term=dasatinib&cond=senescence&rank=1

Clinical Trial (Mayo Clinic): Senescence in Chronic Kidney Disease

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https://www.ncbi.nlm.nih.gov/pubmed/20619334

Anti-ageing and rejuvenating effects of quercetin.

Abstract

Homeostasis is a key feature of the cellular lifespan. Its maintenance influences the rate of ageing and it is determined by several factors, including efficient proteolysis. The proteasome is the major cellular proteolytic machinery responsible for the degradation of both normal and damaged proteins. Alterations of proteasome function have been recorded in various biological phenomena including ageing and replicative senescence. Proteasome activities and function are decreased upon replicative senescence, whereas proteasome activation confers enhanced survival against oxidative stress, lifespan extension and maintenance of the young morphology longer in human primary fibroblasts. Several natural compounds possess anti-ageing/anti-oxidant properties. In this study, we have identified quercetin (QUER) and its derivative, namely quercetin caprylate (QU-CAP) as a proteasome activator with anti-oxidant properties that consequently influence cellular lifespan, survival and viability of HFL-1 primary human fibroblasts. Moreover, when these compounds are supplemented to already senescent fibroblasts, a rejuvenating effect is observed. Finally, we show that these compounds promote physiological alterations when applied to cells (i.e. whitening effect). In summary, these data demonstrate the existence of naturally occurring anti-ageing products that can be effectively used through topical application.

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https://www.ncbi.nlm.nih.gov/pubmed/25754370

The Healthspan of Mice is Enhanced by killing senescent cells, using Dasatinab (Sprycel) and Quercetin.

Abstract

The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, WHICH SELECTIVELY KILL SENESCENT CELLS.

By transcript analysis, we discovered increased expression of pro-survival networks in senescent cells, consistent with their established resistance to apoptosis.

Using siRNA to silence expression of key nodes of this network, including ephrins (EFNB1 or 3), PI3Kd, p21, BCL-xL, or plasminogen-activated inhibitor-2, killed senescent cells, but not proliferating or quiescent, differentiated cells.

Drugs targeting these same factors SELECTIVELY killed senescent cells.

Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs ("mouse embryonic fibroblasts").

In vivo, this combination reduced senescent cell burden in chronologically aged, radiation-exposed, and progeroid Ercc1delta mice.

In old mice, cardiac function and carotid vascular reactivity were improved 5 DAYS AFTER A SINGLE DOSE.

Following irradiation of one limb in mice, A SINGLE DOSE led to improved exercise capacity FOR AT LEAST 7 MONTHS FOLLOWING DRUG TREATMENT.

Periodic drug administration extended healthspan in Ercc1delta mice, delaying age-related symptoms and pathology, osteoporosis, and loss of intervertebral disk proteoglycans.

These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.

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Ellis: In the treatment for leukemia, the patient takes the pill for the rest of his life, and this controls this specific kind of leukemia for they don't know how many years... it used to be fatal in 3 to 7 years.. now they have people leading very normal life after 12 years... if they take it every day, for many years, the side effects must not be so terrible... the worst side effect, it seems to me, is that it drops red and white blood cell... but that can be reversed easily, and in any case, I think it won't happen in three days of Sprycel or Tasigna. So...

see: Sprycel Side Effects . Tasigna, side effects

Leukemia patient, Gary Gonzalez, talks about "side effects" of Tasigna (nilotinib) (from 3:06 to 4:00)

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Dr. Judith Campisi, Buck Institute for Research on Aging, lecture on "Senescent Cells, Cancer, and Aging"


"It’s almost an embarrassment of riches to be having conversations about how whether one drug is more wonderful than the last."

For 10 years, Gleevec has been the closest thing to a cure for CML. Touted as a breakthrough, the drug has lived up to the hype. Deaths from CML dropped from 10 to 20 percent a year to 1 percent, says Hagop Kantarjian, MD, chair of the department of leukemia at M.D. Anderson Cancer Center in Houston.

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etoussier@safe-mail.net
Ellis Toussier

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Table of Contents | Consult with Ellis Toussier (re: Good Nutrition, Anti-Aging Therapies) | Diabetes Made Simple | The Glucose Theory of Aging | Assess Your Pancreas... | The Anti-Aging Anti-Diabetes Diet... | The Carbohydrate Thermometer | 10 Typical Glucose Tolerance Test Results | Hb-A1c to Mean Plasma Glucose Conversion Table

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This page created November, 2018