Introduction to senolytics

Hi everyone, 

The term "senolytics" refers to compounds that selectively induce cell death in senescent cells. 

Senescent cells are cells whose metabolism has gone awry for one reason or another, often due to DNA damage. The metabolism of these cells involves secretion of inflammatory molecules. These cells do not function and divide properly, and are considered by some researchers to contribute to age-related inflammation, increased cancer risk, and possibly a shortened lifespan.

One remarkable study published in 2015 reported that the chemotherapy agent dasatinib, and the plant flavanoid quercetin, were effective senolytics, selectively eliminating different types of senescent cells in mice. 

Please share your thoughts on, and experiences with, senolytics here! 

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  • I am just preparing to begin a C+D protocol. I am going to take based on my weight of 180 pounds 200 mg of Dasatinib and 2000 mg of Quercetin. My protocol will be two rounds, one week apart. I will advise of my experience after starting the protocol. There are lengthy accounts of experimentation on a number of longevity sites such as LongCity.org .

    Like 1
      • Viperml
      • Viperml
      • 4 yrs ago
      • Reported - view

      David Michel 

      Hello David,

       

      How are your results? How did you get Dasatinib? Did you participate in the group buy on longcity that purchased it? 

      Like
  • What Compounding pharmacy carries the dasatinib?

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  • I have called two compounding pharmacies looking for dasatinib. But no luck finding the inexpensive source.

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      • Brennan
      • Brennan
      • 4 yrs ago
      • Reported - view

      Kerry Thankyou! Keep me updated and I will do the same as I am also looking.

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  • A future alternative to the C+D senolytic treatment (which has some concerning side effects) is the DNA approach to clearing senescent cells.  A Seattle-based bio-startup called Oisin Biotechnologies has sequenced a plasmid (a ring of DNA) that is encased in a lipisome (a lipid bubble) for delivery inside cell walls.  The plasmid/lipisome is suffused into the bloodstream and enters most cells.  The plasmid is sequenced to detect whether the cell is senescent, as determined by whether it is generating transcription factors to express the protein p16.  If p16 expression is detected, the plasmid triggers a "suicide gene" that causes the cell to go into aptosis, to neatly disassemble itself, and to disappear.  The same Oisin technique can detect and induce aptosis in malignant cells that are expressing the cancer-signal protein p53.  I wrote a column about this for Analog Magazine, which is available HERE.

    The Oisin technique is presently being tested on aging mice (see LINK), and the ongoing tests have so far has shown that with the best treatment the mice become visibly healthier and live longer.  There are no known side effects to this senescent cell clearance, except for possible wound-healing delay and pregnancy complications.  There are currently plans for tests the Oisin technique on other animals and on humans, but it will be some years before the treatment is generally available.

    Like 4
      • Dan Nave
      • Dan_Nave
      • 3 yrs ago
      • 1
      • Reported - view

      JGC 

      Great article in Analog.

      Like 1
  • I have purchased Dasatinib through Medimpex, a India phara supply company.  I deal with an individual named Soni-Jan.   I have purchased both Rapamycin and Dasatinib through this company.  Seem to be legitimate however since I have not assayed their products I can't say for sure, however doing searches on the specific products I have purchased they appear to be legitimate.   Now my purchase of Dasatinib was made through MedImpex.  I purchased a 20mg bottle of 60 capsules for a total of 189.00 plus 25 dollars express EMS shipping.  I purchased this last year but have waited to find the results of the recent study.  At the recommenced dose, for my weight, I will have to take 200 mg Dasatinib and 2000 of Quercertin.   My purchase thus yields enough Dasatinib for six dosages.   or two every 6 months.  Below is a photo of the Dasatinib box.  I have been out of the country and plan on start the first week protocol soon.

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      • Kevin A
      • Valued_Customer
      • 3 yrs ago
      • Reported - view

      djmichel Hi DJ.  I was hoping you could help me with a question.  I recently ordered the exact same product from Bon Hoa, (60) tabs of 20 mg Dasatinib.  This is what showed up...28 tablets that look like this.  Could you confirm this is the same style tablet that you received in your order?  Just want to be safe. Thanks much  👍

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      • djmichel
      • CDR Phx
      • djmichel
      • 3 yrs ago
      • Reported - view

      Valued Customer 

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      • djmichel
      • CDR Phx
      • djmichel
      • 3 yrs ago
      • Reported - view

      Valued Customer OK the only difference seems to be you have capsules and I have tablets.  

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      • djmichel
      • CDR Phx
      • djmichel
      • 3 yrs ago
      • Reported - view

      djmichel the photo only show 5 but I take ten.

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      • Kevin A
      • Valued_Customer
      • 3 yrs ago
      • Reported - view

      djmichel Thanks DJ.  I really appreciate that.  You're the 2nd person to confirm that.  I may have something different.  I'm suspicious.  Only 28 capsules and they're not tablets

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      • BobM
      • BobM
      • 3 yrs ago
      • 1
      • Reported - view

      Valued Customer 

      FYI, mine are 50 mg, white tabs, no marking on tabs. 

      Like 1
  • Additionally, Medimpex email: Trademedimpes@gmail.com Web Site: http://dropshipmd.com

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  • David

    I found a Medimpex India site from a Google web search, but a search in the site for Dasatinib among their products gives no results.  A search for Dasatinib at the http://dropshipmd.com web site also does not give any results.  Any suggestions?

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  • P.S.  An attempt to send an email inquiry to Trademedimpes@gmail.com just bounced.  Apparently that gmail address is no longer valid.

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  • I had the wrong email address listed, it is: trademedimpex@gmail.com . They do not list Dasatinib on the web site, email them for a quite. Sorry for the original typo.

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  • The following post that I originally placed under "Self-Experimenting/Share" may be a better fit here! "I mentioned the senolytic supplement fisetin under Rapamycin cost and mentioned one of the references. I received my 100mg fisetin caps yesterday ($15/30 Swanson) so commenced a fisetin/quercetin senolytic trial of my own design (not a doc but do have an MS in biochemistry and studied some pharmacology). I tried 1 g (10 caps) of fisetin instead of the dasatinib (based on the planned dosage for an upcoming trial w/ post-menopausal women) along w/ the prescribed ~2g (my weight=165) quercetin recommended in Bill Faloon's RAADFest handout. No noticeable bad side effects since taking at 4pm yesterday and foot pain (likely neuropathic) seems about 30% better along w/ possible increased energy. Planning a repeat dosing in a week as recommended in the Dasatinib/quercetin protocol, but w/ fisetin/quercetin." Fisetin is much easier to get and seems to have fewer side effects, and so far, nice benefit after two years of foot nerve pain.

    Like 1
      • Kerry
      • Kerry
      • 4 yrs ago
      • Reported - view

      Dennis Fink I did 500 mg Fisetin plus 1000 mg Quercetin, to test for issues, two days ago. No noticeable effects. I plan to up the dosage tomorrow.  Have you done your second dose yet? Are you doing it in an empty stomach or with food?

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      • Dennis
      • Retired USAF pilot, biochemist.
      • Dennis
      • 4 yrs ago
      • 1
      • Reported - view

      Kerry I increased my second dose to 1400 mg fis and about the same Quer w/ my bulletproof coffee (butter/cinamon) first thing in the morn. on basically an empty stomach. Better pain relief than the previous smaller dose and it lasted for several days. Dr. Green is using fisetin w/ his rapamycin protocol but I don't know how much yet! Anyone know?

      Like 1
  • I used a referral service in India to seek sources of Dasatinib.  I received several replies, which are summarized in the attached spreadsheet file.  I ended up ordering from BonHoa, and I am expecting delivery in about a week.  I believe that Lucidas Dasatinib is a generic knockoff from the Indian pharma industry, not the original Bristol-Meyers Squibb product, which goes for a rapacious $3k for thirty 50 mg caps. The Medcast entry in the table is probably the latter.

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  • Followup:  My order of Lucidas Dasatinib from BonHoa Pharmacy of New Delhi, India arrived on October 24 (my birthday).  I paid a total of $307 including shipping for 60 tablets of 50 mg Dasatinib (rather better than $2k for 4 tablets!).  Others on RescueElders have used this source successfully and have apparently received the real thing, so I recommend this source of Dasatinib.

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  • I also ordered Dasatinib from BonHoa.  Package was opened by customs, resealed, and delivered in about 2 weeks.  So it is legal, or at least acceptable to our guardians.

    Like 2
      • JGC
      • Retired Professor of Physics
      • JGC
      • 5 mths ago
      • Reported - view

      RobH 

      Ordering prescription-only meds from BonHoa and other suppliers in India is a bit of a crapshoot.  I had a ~$200 order of Dasatinib from the AntiAging Store that was comfiscated at JFK customs on its way to Seattle.  Fortunately, the AntiAging Store shipped me a replacement order at no cost, and that one arrived OK.

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      • MSS
      • Mahabir_Surah
      • 5 mths ago
      • Reported - view

      JGC I have been in touch with a Chemist that I know in India. He told me that he can supply medicines at competitive prices. His name is Naresh Kumar and he can be contacted by email at nkjagsi231@gmail.com He does not have a website. Send an email and he will respond and will provide quote but allow extra time for first order.

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  • Delivered price for BonHoa Dasatinib was $200 for 60 20mg pills.  Enough for 3 treatments.

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  • No matter what senolytic you are taking, it sounds like you should take it in large intermittent doses? I.e. Quercetin is not a once a day supplement like most people probably take it.

    Like 1
      • David H
      • David_Hanson
      • 3 yrs ago
      • 1
      • Reported - view

        Karl I take 500mg of quercetin each day.  Why should I stop taking it daily?  I haven't read that it shouldn't be taken daily.  Thanks.

      Like 1
      • Karl
      • Karl.1
      • 3 yrs ago
      • 2
      • Reported - view

      David Hanson I don’t think there’s anything wrong with taking it daily. I also do. But it seems from what I’m reading, that senolytics probably should be taken in larger bolus amounts? I.e. take 2 grams once a month? I’m more asking a question than making a recommendation.

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    • Karl To get the senolytic effect you need to reach a threshold. if under that threshold level you might have other positive effects but not very much of the senolytic effect. Fisetin might have a geroneuroprotecting effect when taken in smaller daily doses, a few hundred milligrams. But that is not enough for a senolytic effect.  Same goes for quercetin.

      Like 2
  • First link:

    Here is is a very informative update about senescence and the potential of senolytic therapies. By Prof James Kirkland. He starts his talk at 45 min and 50 sec. 

     

    Prof Nir Barzilai gives his talk, starting at 1.35.50. (Also good)

     

    Longevity Science Singapore Conference & Opening of NUHS Centre for Healthy Longevity | PM Session - YouTube 

     

    Next link:

    Prof Brian Kennedy start his short talk at 44,20 and after him comes Prof Matt kaeberlein who starts his talk at 58

    Longevity Science Singapore Conference & Opening of NUHS Centre for Healthy Longevity | AM Session - YouTube

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  • Thank you. Very illuminating.

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