Fisetin, Quercetin & Dasatinib in Clinical Trials | Dr. James Kirkland Interview Series Ep 4
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- Опубліковано 13 лип 2021
- In this video Dr. Kirkland talks about the senolytics that the Mayo Clinic is using in the on going trials, dasatinib, Fisetin and Quercetin. He also talks about the way the work and the schedule to taking them,
Dr. James Kirkland is Director of the Robert and Arlene Kogod Center on Aging at Mayo Clinic and Noaber Foundation Professor of Aging Research. Dr. Kirkland's research focuses on cellular senescence, age-related adipose tissue and metabolic dysfunction, and development of agents and strategies for targeting fundamental aging mechanisms to treat age-related chronic diseases and disabilities and to extend healthspan. He published the first article about drugs that clear senescent cells, senolytic agents. A novel, mechanism-based, hypothesis-driven drug development paradigm was used to discover senolytic drugs. Based on the observation that senescent cells release factors that cause apoptosis of the cells around them, yet are themselves resistant to apoptosis, Dr. Kirkland hypothesized that senescent cells utilize senescent cell anti-apoptotic pathways (SCAPs) for protection from their own senescence-associated secretory phenotype (SASP). Using bioinformatics analyses of senescent vs. non-senescent cells and RNA interference, Dr. Kirkland identified these SCAPs and verified their importance for senescent cell survival. Dr. Kirkland used bioinformatics approaches to identify agents that target key nodes across the SCAP network and demonstrated these drugs are senolytic in rodent and human cultured cells and mice in vivo. These senolytic drugs include Dasatinib (D), Quercetin (Q), Fisetin, Navitoclax, and related compounds. Dr. Kirkland showed these agents delay, prevent, or alleviate multiple disorders in mouse models of human chronic diseases and aging phenotypes. Conditions alleviated in mouse models include frailty, diabetes, hepatic steatosis, cirrhosis, renal dysfunction, neuropsychiatric disorders, dementias, pulmonary fibrosis, osteoporosis, osteoarthritis, retinal degeneration, diastolic dysfunction, cardiac ischemia, vascular hyporeactivity, infertility, and skin disorders, among others. He demonstrated that intermittent, orally administered senolytics reduce senescent cell abundance in adipose tissue and blood markers of senescent cell burden in blood of patients with diabetic kidney disease. He and collaborators found that a brief course of senolytics enhances physical function and reduces frailty in patients with idiopathic pulmonary fibrosis, a fatal, cellular-senescence-driven disease for which available treatments have been unsatisfactory. Multiple clinical trials are currently underway of the senolytics that Dr. Kirkland discovered. He is a scientific advisory board member for several companies and academic organizations. In addition to being President-Elect of AFAR, he has been a member of the National Advisory Council on Aging of the National Institutes of Health, and past chair of the Biological Sciences Section of the Gerontological Society of America. He holds honorary appointments at Boston University and the University of Groningen in the Netherlands. He is a board-certified specialist in internal medicine, geriatrics, and endocrinology and metabolism.
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Please summarize the information from Dr. Kirkland and other experts you interview, specially about very crucial dosages. The matters are so scientific for the non-scientists like myself.
I´ve been taking fistein, quercetin, NAC, and glutathione daily for 6 months. I am doing my own research and I am testing my blood every month from CRP, IL6, liver enzymes, all the works. So far the results are : I feel exactly the same, there has been no noticable effects on anything that I can think about. There are however a few important things I want to say : My blood work is MUCH better than it was 15 years ago. My CRP is half ( from 3.5 to 1.5) and all my liver enzymes and markers are incredibly better ( a HUGE difference). One other thing that is definitely better is that hangovers are now non-existant and I can drink more wine or beer without feeling spacey. I have no clue if what I am doing will bring a good payback or a terrible one, but it is my life and my decision and I am telling you this for all of you interested in the topic. BTW, no change in glucose but a huge difference in HOMA and HC1A. Good luck !
This is ALL POSITIVE. Dr Judy Mikovitas suggested Quercetin also.....I do Quercetin sometimes....with Zinc and Vitamin C and D......I was getting a cold last week and I took Quercetin and my cold was gone in 2 days....
After listening to Dr Kirkland on multiple interviews…I deduced a 3 day on 11 day off cycle. You need sentient cells for wound healing but don’t want old cells just hanging around too long I did just knock out a coronavirus in 2 days (not sure of type) with Q & Zn. I suspect the NAC is effecting ETOH tolerance as I have noticed before. N=1
Add resveratrol, cycloastragenol... You're really missing out if you don't have the dasatinib, but I caution the use of that note than once or it could affect your vision.
What is your dosage of fisetin and quercetin?
@@ivannagy6427 1200mg Q, 1000mg F
Four videos in and getting more and more interesting. Thank you for getting Dr Kirkland to divulge this really interesting information about senecent cells and senolytics.
Many great and new points to learn here, thanks to you both, Dr. Kirkland & Richard!
Hi Susan, thanks
Good discussion of the half life of the senolytics and the approach!
Great information and video. Dr K’s lab sure seems to be taking long time to release the Fisetin study results
Excellent video Richard. You ask the perfect questions and keep things short. I didn't realize quercetine 1/2 life is much longer than the other two, so I might reduce the number of days that I take quercetin. I'll be looking forward to the results of this trial!
Hi Thanks for your comment. I certainly found Dr. Kirkland's way of thinking about the half life and the aim very illuminating. We will also be watching for the outcome of the trial.
In regards to Senolytics, Dr. Kirkland stated:
"We don't know if they're safe. We're messing around with a key fundamental process in life. We don't know the downsides are going to be."
Yet, so many of us are a hit and run fisetin trial on our own (including myself). Though not a subject of this video, the same statements could be made about NMN and NR. Though I think NR has a GRAS notice, but still, its long term effects are unknown.
Thanks Richard; short, sweet and money saving. Will cutback dosage to once a week and 1.5 grams.
Will tell people to tune you in and turn you on.
Hi Elliott thank you, that would be great! I had heard differing stories about schedules and dosages for senolytics like Fisten. I found Dr. Kirkland's description very clear.
Is there a place for transcript of the podcasts?
Merci !
How would they differentiate cell lysis symptoms from direct compound adverse effects? I am assuming there would be a lysis syndrome when the senescent cell die off.
Thanks Richard.
Hi Ron, Thank you!
Dear Richard, thank you for your informative videos. Very glad I saw this one in particular, as I‘ve been supplementing with Quercetin (500mg per day) since 2 weeks. Now going to stop taking it. Thanks for your work 🙏🏽
Why are you going to stop taking it?
Very detailed, Strawbeerry and apple I know it contain fisein, I didn't know cucumber.
Hi Sparkling thanks for comment
The body is extremely conservative with protein also in aged flesh there is a lack of energy to metabolism of protein.
In the young the immune system removes old cells....
In the old the immune system is reduced by invaluation of thymus and senescence in white blood cells...
Rather then posion cells its probably easier and more effective to restore the immunity to them
Hi Matt, Thanks for your comment. I do see your point, however, how do we restore the immune system? If I understand Dr. Kirkland correctly it is all linked together and by reducing senescent cells we will boost the immune system and poisoning senescent cells does not seem to have many detrimental effects.
We do intend to look at the immune system in more depth, and certainly I would agree if we could figure out how to get the immune system to clear the cells that would be best.
@@ModernHealthspan the trimm trial reversed to a large degree immune invaluation
By Hgh and zinc and dhea,
The also used metformin to limit blood glucose....
I produce Hgh by fasting and because when I'm fasted there's no glucose....no need for metformin...
Anyway I also keep glutathione above optimum with several grams of gly/nac......
Although spermidine is said to be sentilitic..I think it's a tool our body uses to manufacture the protein into little machines
Will see where it takes me
I get at least 36 MG a day
There is some evidence in being nutritionally ketogenic to improve T4 cell & improve immunity. I also think eating organs may be a missing link but I can only handle desiccated!
Richard, you ask good questions!
Thanks JC
Rimon of wellness messiah explained the flaws in the UTP study that found no senolytic activity of fisetin. Among the several flaws was a dose that was much too low to be effective. In humans the effective dose is 20 mg per kg of body weight. Rimon showed how he did the calculation for the equivalent dose given in the mouse studies ITP performed. It was a small fraction of that.
Having senolytic cells is not recognized as a disease. It is recognized as undesirable in large quantities. The quantity increases with age. Those studying this food component are generally interested in lifespan and health span extension and age reversal. In addition to fisetin's hoped for senolytic effect it is also said to be a Sirt1 and Sirt 2 activator. Quercetin has multiple benefits as well. It gets zinc through the cell membrane into the cytoplasm where it can kill viruses. In this respect it requires twice the dose of hydroxychloroquine. It is also one of two molecules that stimulate NAMPT a critical enzyme in the salvage pathway for the efficient recycling of NAD+ (the other being R- alpha lipoic acid. There are two other factors in the pathway to be dealt with.)
I hope Dr. Kirkland takes this into account in his study of fisetin.
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Did he say the dosing for Quercetin? A little concerned at the end when he suggested we didn’t know the downside of taking these drugs. Like that they don’t stick around. Probably not something to be taking every day.
Hi Scott, thanks for your question. Dr. Kirkland did not say the dose for Quercetin, but looking at some clinical trials we can see 1000mg for 2 or 3 days followed by 2 weeks or 28 days off.
clinicaltrials.gov/ct2/show/NCT04313634
clinicaltrials.gov/ct2/show/NCT02848131
clinicaltrials.gov/ct2/show/NCT04685590
But he did say that they were using a hit and run approach of taking them every two weeks or a month.
On one of Dr. Brad Stanfield's vids he said 500mg of Quercetin with 100mg of disatinib for three consecutive days only
Thank you for this. It appears from this video that dasatinib and quercetin act separately on different cells. I presume that the drug and supplement do act synergistically. If this is the case then dasatinib and quercetin could be taken separately or together at different times. Is this correct?
Hi Stephen thanks for the question. I agree with your conclusion. Dr Kirkland said that they acted on different cell types and I have not heard that there is any synergy between them. I can see why if you are running a trial you would have people (or mice) take them at the same time as it would reduce management. Having said that, I can find no trial where they were used together but at different times.
@@ModernHealthspan Thank you, Richard, this helps. For my chronic myeloid leukaemia (CML), dasatinib works very satisfactorily in inhibiting the kinase Bcr-Abl1, however, I understand that dasatinib is a broad-based kinase inhibitor that is known to target up to 30 kinases. I suspect that the kinase of interest here is Src (like "sark"). The flavonoids, on the other hand, appear to target different kinases. Presumably, in time, targeted kinase inhibitors will be manufactured to replace the flavonoids.
@@sterlingtimes I discovered this totally by co-insedense ,I did not fully believe the Rick simpson story" Phoenix Tears"
Ginger ginger ginger
Please find something for Long Covid. I am sick for two years. 😢
I'm using Fisetin, Dasatinib and Quercetin on an intermittent dosing protocol.
How do you get Dasatinib?
@@KJ-um1gq
I have a doctor's script
What's the outcome?
Thanks Richard, just to make sure, how should the fisetin be taken? 3 consecutive days with 20mg per kilo? Every month?
Lol he told you you shouldn't be taken them
Here are my research findings: Dasatinib plus quercetin protocol works to reduce cellular senescence. Patient with GFR of 57 was off of allopurinol and has GFR of 89 holding 1.5 years post trial. Patients that fasted before and after administration had higher level results, such as drastic adipose fat loss. Patients that consumed food within 4 hours each side of a dose had negligible results. Apparently food competes with absorption. Lungs and fatty liver were reduced. The negative side effects: during peak plasma patients experienced mild fever and headaches. Long term side effects were related to vision. This suggests that due to the diffusion nature of ocular cells rather than circulatory exchange they may rely on senescence for longevity. In my opinion from the data and observations it suggests that the D+Q+F protocol is beneficial if administered as a one time "reset" and targeted to ages 30 and above, but most effective between 35 and 45. Hypothesis: may be highly effective in treating nephritis, fatty liver, preempt most breast cancer, Crohn's, and age related uterine issues. The fasting group that used NMN during the 1 month post trial found better results than DQF only. Would be interested if other researchers find similar results. Hypothesis: DQF+Fenbendazole+ADEK&B-complex for treatment of colon/bladder/prostate cancers.
Interesting. So you’re a physician?
Thanks
Is it better to take fisetin 20mg/kg body weight once in a day? Or should I half that and take it two times or divide by three and take it three times? Best time of day? Combination with something else to target things like plaque?
I was watching a video of Dr. David Sinclair the other day where he mentions that he takes 500 mg per day as maintenance dosage.. But in Dr. Kirkland’s clinical trials, they have dosed subjects with 20mg/kilo.. and given the half life is pretty less, both should be fine..
So, I have fisetin capsules I was hoping to help with Peyronie's. Does this mean I should discard and not use the fisetin or should I pair it with something else so it replaces the fibrous tissue with new cells and not fibrotic collagen?
I have sclerotic tissue...scarring. I have not heard of anything that will reverse scar tissue. Once your body produces it there isn't a reversal. I did read silica and selenium will soften it but not reverse it. I was hoping Fisetin would help my scar up legs but I don't think it will. It will stop further damage. That's a good thing.
He states “People should not be taking these drugs. Physicians should not be prescribing them. We’re messing around with a key fundamental process in life.” And “we’re aiming at people with serious conditions and looking at safety.”
IMO he’s overdoing it a bit with the safety advice. Fisitin and quercetin are naturally occurring flavonoids and have been shown to be safe up to regularly high dosage (100 mg/day) on a regular basis.
People with serious conditions are likely to die soon and all of us are aging and are going to die in the next couple of decades, so me, personally, I’m willing to take the risk and try out F + Q with some olive oil for better absorption.
I don’t expect to live forever because of it, but I’m also not worried about the possible downsides.
It’s a bet I’m willing to take.
The problem is that they don't have good specificity, even fisetin. So how many good cells are killed per senescent cell when using their protocol?
I guess that's why he was emphasising that it's a hit and run thing. Clear out the senescent cells and then stop. Any impact on the rest of the body would only be temporary and healthy cells can be replaced as normal
@Ernie H What?
@Ernie H Fisetin could eventually kill way more good cells than bad ones, and some organs don't have much regenerative capability, like the heart and brain. Chemo is definitely not the panacea and is used as last resort when people's life is endangered.
Hello.
I am a female in my 40's, 50kg of weight and took 1000mg of fisetin for 2 days. Initially I felt very tired and drained and a bit of headache, also my heart beat harder than normal, sometimes pumped quite hard for couple seconds. Its been 4 days since I stopped taking it but still feeling a bit tired and my chest feels a bit stuffy. Is this normal? I have been told it would be safe.
Are you feeling better now Ann?
@@picer oh yes thank you.
After some research I suspect elevated heartbeat was due to lack of oxygen in my body. Probably high dose of fisetin consumed more oxygen and water to do its job. Then after I took hight dose of vitamin C, the stuffy chest feeling and elevated heart beat had disappeared. So probably vitamin C helped to carry and provide oxygen into my body.
I had unusual side effects probably because I have chronic sinus infection and stuffy nose all the time so I have trouble of getting oxygen into my body.
@@annlee4704 fisetin stimulates autophagy, so probably what you have experienced are autophagy symptoms
@@annlee4704 Hope you’re feeling better. For chronic sinus try elderberry and/ or bromelain supplements. Both will help very fast.
So, those drugs won't be available over the counter. We will have to kneel in submission to the physicians who will have control over our lives. Better than nothing though...
Hi Cybair, thanks for your question. Quercetin and fisetin are available over the counter. Dasatinib is indeed a prescription drug.
Fisetin costs about $30 dollars a KILOgram, unless you want to buy it in bulk. One seller is a company called sciyu, that sells on Ali Baba.
Quercetin and fisetin are NOT drugs...they are nutrients!
"Life extension" has quercetin and fisetin.
@@paulwolf3302 you would trust something from Ali Baba?
Hmm, an "Apple a Day", who knew..............
Hi thanks. Yes, just remember to eat the peel!
@@ModernHealthspan make sure it's organic or find out the hard way with all the pesticides
@@jeffmorabito10 and remove pesticide film. Many times apples are stored for up to a year in storage warehouses.
@@jeffmorabito10 "organic" is a scam.
Did this interview change your view on Fisetin and Quercetin? I.e.have you reduced your intake from daily to monthly?
Disregard most everything Mayo Clinic puts out!
This is such a terrible title for views lol. Should say smth like ¨Rejuvenating therapeutics (Dasatinib, Fisetin, Quercetin) already in clinical trials!"
Terrible speakers.
Welcome to discord.gg/ztPFMuKu to discuss all the longevity regimens.