#1

The young African turquoise killifish has a high regenerative capacity, but loses it with advancing age, adopting several aspects of the limited form of mammalian regeneration. We deployed a proteomic strategy to identify pathways that underpin the loss of regenerative power caused by aging. Cellular senescence stood out as a potential brake on successful neurorepair. We applied the senolytic cocktail Dasatinib and Quercetin (D + Q) to test clearance of chronic senescent cells from the aged killifish central nervous system (CNS) as well as rebooting the neurogenic output. Our results show that the entire aged killifish telencephalon holds a very high senescent cell burden, including the parenchyma and the neurogenic niches, which could be diminished by a short-term, late-onset D + Q treatment. Reactive proliferation of non-glial progenitors increased substantially and lead to restorative neurogenesis after traumatic brain injury. Our results provide a cellular mechanism for age-related regeneration resilience and a proof-of-concept of a potential therapy to revive the neurogenic potential in an already aged or diseased CNS.

https://www.nature.com/articles/s41536-023-00304-4

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#2

Thx for sharing this. Has anyone on this Forum tried a D + Q protocol? I think one that is being used in clinical trials for ALS and other neurodegenerative conditions is uses is 2 or 3 days of 100mg D and 500 or 1000mg of Q every other week for 6 weeks.

Anyone?

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#3

We have a few threads discussing this, with some people having done it:

Here: Senolytic Therapy: What are you doing?

Here: Fisetin - The Mayo Clinic Senolytics Protocol?

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#4

Sorry - I missed these in a search. Awesome- thanks!

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#5

I have done a several rounds of D & Q. I take 100mg dasatinib, with 1gm quercitin. The first was in 2022, which was a single dose prescribed by a dr. The second was in 2023, single dose, prescribed a another dr. In 2024, I obtained dasatinib without a rx from India, and followed the 3 day protocol instead, once a month. I completed 3 days of D&Q, waited a month, then repeated it again for 3 days. A month has passed since the last round, so I just did the first day, and woke up with alot of swelling on the left side of my face. This had never happened before, and I read that it has been a rare side effect, since D can cause fluid retention. I wonder if anyone else on this forum has had this side effect? I also had some mild nausea which I had not experienced before. I took it before bedtime, so perhaps taking it much earlier in the day would help prevent these sides. I am hypertensive, so I take Losartan, hydrochlorothiazide, and also atoravastatin for lipidemia.

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#6

cronoslogical, Iā€™ve been doing the D + Q 3-day protocol every three months for two years an hour before breakfast using coffee with olive oil blended in it. I also blend the Quercetin into the coffee because it can irritate an empty stomach in capsule form. An hour after this I will have breakfast. Iā€™ll commonly go ahead and take any supplements I normally take with breakfast because the D + Q will have been absorbed within that hour. Any medicines I need to take would be placed an hour before the D + Q protocol or delayed for later in the day. Other than a mild laxative effect I have never noticed any side effects for this protocol.

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#8

Are you aware of any positive effect from the D+Q protocol?

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#9

Ulf, I donā€™t notice anything, but I continue based on the research assuming there may be some long-term benefit. And, itā€™s an easy protocol to follow.

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#10

IIRC the mayo protocol did 3 weeks of 3 days, is there a reason why you do only 3 days per quarter?

#11

Here is a chart from copilot.microsoft.com summarizing different protocols, but Iā€™m sure there are others. My protocol isnā€™t listed, but if I try another AI Chat program it would probably appear. I donā€™t recall exactly where I got my original information years ago. If you want to know the specific source of a given protocol type it into ChatGPT (or another AI program) and ask for the source of that protocol.

Protocol Medications/Supplements Dose Days to Take Frequency Repeat Cycle
A Grape Seed Extract (GSE) + Fisetin 2000 mg GSE, 1000 mg Fisetin 3 days Once Every 4 weeks
B Grape Seed Extract (GSE) + Fisetin 4000 mg GSE, 2000 mg Fisetin 3 days Once Once a month for 4 months, then 1-2 times a year
C Dasatinib + Quercetin 100 mg Dasatinib, 500 mg Quercetin 3 days Once Every 3 months
D Dasatinib + Quercetin 100 mg Dasatinib, 500 mg Quercetin 3 days Once Once a month
E Fisetin alone 2000 mg 3 days Once Every 4 weeks
F Quercetin alone 500 mg 3 days Once Every 3 months
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#12

Thanks. In 2 years, have you seen changes in your bioage markers? Why did you choose that protocol? I started the protocol used in the pulmonary fibrosis study, which is 3 days of D&Q per week for 3 weeks. There are several protocols, and the results regarding the effect of D&Q on markers of senescence vary.

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#13

Can anyone point to a study on humans showing positive results from D+Q? It may very well exist I donā€™t want to discourage use, but I canā€™t find one. There was a first tentatively positive study on idiopathic pulmonary fibrosis, but a follow-up study did not replicate the findings however it was under-powered https://scholars.uthscsa.edu/en/publications/senolytics-dasatinib-and-quercetin-in-idiopathic-pulmonary-fibros

A study on bone health for menopausal women showed no difference in primary outcome between D+Q and controls, and neither in secondary outcome at the longest time point 20 weeks, except (possibly) for a subgroup with the highest senescent cell burden

But I may well have missed something!?

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#14

I agree; the positive results I have seen from D&Q studies have been quite limited. I only found mention of D&Q ā€œreducing the burden of senescent cellsā€ in a couple of studies. I will have to research some more to find out which markers this protocol affects so that I can assess its effect. Only markers such as alkaline phosphatase, C-reactive protein, globulins, etc which are available to those of us who are not researchers are available for testing, therefore the info we can get about the effects of these protocols is limited, since there are other proteins and measures of senescence that we do not have access to.

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