Senolytics and Female Fertility

Does anyone know how senolytic therapy could impact female fertility? While the theory that women start with a finite amount of eggs which simply dwindle over time until fertility is depleted has been longstanding, newer research points to the possibility that stem cells nests in the ovaries might be able to produce new eggs.  Has anyone read anything about his or have you seen changes in your fertlity after senolytic (or other anti-aging) therapy?

Might a senolytic therapy boost stem cell nests in the ovary by eliminating general SASP or senescent cells in the ovary itself.

I wonder if currently available senolytics could impact the senolytic ovary cells, as in do senescent ovary cells undergo apoptosis by the mechanisms of currently available drugs and supplements?

Thank you!

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  • About a month ago I began taking 3 day doses of senolytic combination every other week; three total treatments so far for possible protection from early dementia (Fisetin, myrecetin and quercetin).  I'm menopausal and have been taking HRT for almost 2 years.  If I miss any HRT doses, I start having severe menopausal symptoms.  I can't be sure it is the treatment that did this, but I haven't changed anything else in my routine.  I chart temps and LH surges.  My body has been aggressively trying to ovulate with all the symptomology of a young lady, except that ovulation has not yet occured according to LH strips and thermal surge.  I have not touched any HRT since I started noticing these symptoms a few days after the first dosage.  If I'd tried something like this in the past, the lack of estrogen from patches would cause severe menopausal symptomolgy, but nothing.  Because if this dramatic shift, I believe that one or more of these particular supplements may have caused senescent ovarian cells to die, which may have resulted in fresh new eggs being produced from ovarian stem cells.  I should also note, that in between the treatments, I take nicotinimid riboside as rejuvenation therapy, though unlike the senolytics, this is not new.  I've taken this on and off for 3 years.  Due to these physiological changes, I'll be combing the scientific literature for information on how these may affect reproduction.  On cursory glance, there isn't a lot of work...all with other mammals, and some is a bit conflicting, indicating species specific effects that may not translate to people. But it seems  like one or more of these may affect reproductive hormones in both women and men.  Personally, I believe this could be an area that could use immediate and prompt interest from reproductive aging researchers doing work on oogonial stem cells and general aging of the female reproductive system.

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    • Self Hacker Lynn 

       

      Now you made me curious. I think you are the first person in here to add myricetin to a senolytic Fisetin and quercetin combination.

       

      May I ask you about why you have myricetin as a key component in you senolytic combination? We have talked about myricetin in here but so far I think you are the first person to use it in a self experiment aiming at reducing senescent cells. I am very happy to hear more about this way of using myrecitin and learn about this approach. 

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    • Staffan Olsson 

      Hi, so originally I added the myricetin because I was taking these for cognitive protection against dementia as I mentioned above, and myricetin protects from glutamates negative effects on brain senescence.  I'm not certain it is an effective senolytic though.  I saw one research report where it wasn't and another that said it had some effect.  Here are some papers:  Iyer SC, Gopal A, Halagowder D. Myricetin induces apoptosis by inhibiting P21 activated kinase 1 (PAK1) signaling cascade in hepatocellular carcinoma. Mol Cell Biochem. 2015;407(1-2):223-37.  

      1. Huang H, Chen AY, Ye X, et al. Myricetin inhibits proliferation of cisplatin-resistant cancer cells through a p53-dependent apoptotic pathway. Int J Oncol. 2015;47(4):1494-502.
      2. Huang H, Chen AY, Rojanasakul Y, et al. Dietary compounds galangin and myricetin suppress ovarian cancer cell angiogenesis. J Funct Foods. 2015;15:464-75.
      3. Life extension article that mentions effects of myricetin in more detail https://www.lifeextension.com/magazine/2017/4/geroprotectors 
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    • Self Hacker Lynn BTW, there are many scientific papers that show myricetin induces cancer cell apoptosis, probably through negative affects on mitochondria and various other pathways like blocking angiogensis in several kinds of cancer cells... bladder, gastric, hepatocellular, cervical, esophageal, colon,  thyroid, osteoblastic, pancreatic, skin, and liver.  Whether this translates to scenescent cells is far less certain.  The effects seem cell type specific with an emphasis on cancer cells.

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    • Self Hacker Lynn 

       

      Thank you for sharing your thinking about myricetin. Myricetin is something I will add to my regim later. it seams to be a promising geroprotector. Actually I should have incorporated it already but decided to start with ferulic acid first. 

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    • Self Hacker Lynn 

       

      Hi again.

       

      I wonder if you can share how much fisetin, quercetin and myricetin you take. And also what the  brands are. I ask this question just beacuase there are a few different formulas of the substances you use.  Best regards 

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    • Staffan Olsson 500mg Fisetin -Novusetin,  200mg myrecetin- source naturals, Activated quercetin source naturals 1g.  All are taken one time per day at night for three days every other week for 3 months.  Currently on 4th treatment. 

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    • Self Hacker Lynn Hi Lynn.  Since female sex drive tends to increase during ovulation, one wonders if senolytics might be a possible treatment for menopausal loss of libido.

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    • Gavril Villiamovich Given my experience, I would say definitely one of these compounds has a substantial effect on libido, though I'm not entirely sure which, and must also admit, that it could be any combination or all three.  I would have to self experiment with one at a time, which I can't do right now. 

      That said, I'm less convinced that the ovulatory symptomology is because of spontaneous production of new follicles or maturation of follicles via senolytic die off of old cells being replaced with new, though this is still a possibility.  My lit search indicates that at least Myricetin, and probably each of these, directly affect sex hormones.  One study on bovine granulosa cells (egg helper cells) showed that myricetin increases estradiol production, and exceptionally so in the presence of IGF1.  In this case, the effects I experienced could simply be due to large increases of estrogen.  In another study, uterus weights of rats increased following myricetin supplementation in food.

      As an aside, apparently low dose MYCE improves human sperm motility, viability & capacitation. - Aquila et al.2012 ...Molecular Repro & Devl. 80:2. 

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      • Aka Loo
      • Aka_Loo
      • 1 yr ago
      • Reported - view

      Self Hacker Lynn Hi! Could you tell us how often you repeat these treatments?  For HRT are you on the Wiley protocol? When do you stop taking the HRT, or could you completely stop it if you repeated these therapies enough? I just started the Wiley but have been on BHRT for close to 5 years. I'm 50. I do not take HGH. I'm thinking about it but have not started it. I was going to try ovarian PRP to try to wake up my ovaries and at least temporarily get off HRT but I don't think that the results are very effective according to what I have read.  

      For other anti aging I was on Metformin but it turns out that my blood sugar levels are way too low to be on it and it had greatly affected my eye sight.  I went to see Dr Alan Green in Queens who does a lot of Metformin and Rapamycin and he told me to get off of it and put me on a weekly dose of Rapamycin for long term anti aging. He told me to start on senolytics to get my ovaries going again- if possible at all. He was also mentioning that to really make it work the HPO axis would have to be back in full function. 

       

      I'm also on the NAD+ patch once weekly. Not sure if that works much. I wish I could do the IV drip. I used to take the sublingual powder. Maybe I'll go back to that- though the taste is not very pleasant. 

      I'm new on this forum but I feel like I'm learning a lot already so wanted to share. :)

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    • Aka Loo TBH, I wasn't able to acquire Myrcicetin during covid, so haven't taken it for many months until 2 weeks ago.  I took 3 days of it and then returned to HRT, because my estrogen has gotten so low hot flashes began.  TBH I take the HRT variably, as I notice the recommended E dose is too high for me, so I take it les.  Take the P about 12 days a month only.  Started NMN powder about 4 months ago.  I like it.  Frankly my guess is that no new follicles get produced, I think instead improving the environment in a multifaceted way restores function of what little is left.  I've not done PRP, but have read it last 2-3 months.  Seems pretty expensive for such little effect.  I've never done M and R so can't speak to those.  BTW, earlier this year, because I couldn't get the M, I was taking only Quercetin and Fisetin.  These did not improve E or RF in any way that I could tell.  So I'm left with these thoughts from what happened at the end of last year, either Fisetin is the key ingredient and will work on its own, or none of these were instrumental, and it was a re-awakening of the reproductive system - which can happen in the fall for some women, or it is critically the combination of all three that has a positive effect.  Personally, I'm leaning toward the middle of these three explanations, with the first as a close second.

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      • Aka Loo
      • Aka_Loo
      • 1 yr ago
      • Reported - view

      Self Hacker Lynn 

      Interesting, I wonder if some of this stuff isn't just good for a certain amount of time? As in when I used to take Metformin at first I was ovulating, but that stopped maybe after a couple of months I think. Same thing with Rapamycin, it is supposed to help with women's fertility for only a short period of time I think. 

      I am going to try the combination that you had used and see what happens. 

      What about the pituitary gland? What is there to stimulate that to make it help ovaries to wake up and function?

      I recently started the Wiley Protocol for BHRT. I had to stop within a month. Either I was on too low a dosage (I probably was) or I just could not absorb well enough topically. I don't know, I have never taken progesterone topically before and I did not feel like it did much for me all together as I started to have really bad hot flashes and sleep issue etc. 

      This sucks basically, to have to play around with all this stuff because your body is not functioning by itself optimally anymore. I wish they could just come up with a pill or shot to keep it all working like it used to, who needs a steady decline in quality of life for like 4 decades? 

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      • David C
      • David_C
      • 1 yr ago
      • Reported - view

      Self Hacker Lynn You need to take Fisetin properly for it to have an effect. The minimum I would say is 2g all at once and repeat a couple or 3 days. 3g is perfectly safe and higher and I generally take 3g. My feeling is that ifyou notice nothing from Fisetin the dose is probably too low

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      • David C
      • David_C
      • 1 yr ago
      • 1
      • Reported - view

      Aka Loo The body can adjust for excesses of certain substances and you get effectively a tolerance. 

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      • Aka Loo
      • Aka_Loo
      • 1 yr ago
      • Reported - view

      David C So take Fisetin 2g for 3 days straight every week or take a 3g dose once a week? Is this supposed to be cycled or do it continuously every week?

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      • David C
      • David_C
      • 1 yr ago
      • 1
      • Reported - view

      Aka Loo No if you do larger doses (which I think is best) then I would do 2-3g for three days straight and then wait a month before repeating. The quickest you want to repeat (from my person experience) is every 20 days or so. Every month is fine and even taking a break for 2 months here and there is not a bad idea. If FIsetin is clearing senescent cells then monthly or even every 2 months should be more than fine. Although I have a feeling that Fisetin suppresses SASP and eliminates to some extent senescent cells as well, like it either kills them off or interferes with them by muting SASP signalling for a time. Then you would have the case to take it chronically. But all data I see suggests it removes cells as the main mechanism. 

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      • Aka Loo
      • Aka_Loo
      • 1 yr ago
      • Reported - view

      David C I will try that! What brand of Fisetin do you use? 

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  • I take Fisetin alone, it has a tremendous affect on what feels like hormone levels. I take 3g of Fisetin for 3 days straight and repeat every month. Single biggest change in my life was after I started doing this. 

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  • All I can say is, after successful aging reversal, my libido reverted back to when I was at least 10 years younger. Not necessarily a good thing you understand. But that's what I noticed. 

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  • First off to everyone who participated in this this thread. Thank you for sharing your knowledge.....but Phoenix who started thread "Senolytics and Female Fertility" I was under the impression she wanted to know if anyone was able to increase their fertility and get pregnant (that's how i read it).... This is what i m interested in.  Has it worked for anyone here?
    Phoenix did you try to use Senolytics to raise up your fertility and get pregnant? 

    Other women seem to have used senloytics to deal with menopause symptoms and get up libido, which is awesome, none to do with fertility or getting pregnant.

    Male members are welcome to share their knowledge! please do

    1) Can anyone here answer Phoenix ' specific question she posted - namely did anyone see improvement in their fertility and/or helped getting pregnant?

    If you have any finding or research papers on this matter will you share on this matter? Very interested in the theory how senolytics can improve fertility and raise libido

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