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
      • 11 days ago
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      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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  • 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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