Attempts to Reverse Aspects of Ovarian Aging

Fertility clinics, just like "anti-aging" clinics, are a lucrative niche industry that has the potential to stop being sketchy and fraud-ridden just as soon as reliable rejuvenation therapies arrive on the scene. Given this, one might view these and a number of other similar industries as potential pools of funding to help bring the first rejuvenation therapies to the clinic. That has to be balanced against the bad publicity attendant with doing business in this part of the market, but considered in the long run, if the therapies work then will even justifiable initial skepticism much matter? The Society for Rescue of Our Elders and Betterhumans trials of senolytic drugs to clear senescent cells are one example of a faction within the highly dubious "anti-aging" marketplace starting to embrace an approach that actually works.

Today's topic is ovarian aging, and the desire to turn back all of the reproductive and metabolic changes that come with it. A variety of interesting efforts on this front have emerged in recent years. You might recall that researchers engineered artificial ovaries and demonstrated them to be fully functional in mice earlier this year, for example. The transplantation of young ovaries into old mice has been demonstrated to extend life and improve health. Over at the SENS Research Foundation you'll find a fairly science-heavy article from a few years back that covers these and other initiatives aimed at postponing menopause.

Here I'll point out news from Inovium Rejuvenation, which seeks to apply the lessons from parabiosis studies to restoring ovarian function in older women. It is an attempt to adjust the balance of signals in the bloodstream towards a more youthful level, something that is also in the process of being trialed by groups such as Alkahest and Ambrosia in the US, though with different goals, different implementations, and measuring different outcomes. My expectation is that likely best plausible outcome, somewhere down the line, is something akin to the results of first generation stem cell transplants - a modestly beneficial override of age-related changes in inflammation, stem cell activity, and so forth. Given the degree of conflicting evidence on parabiosis from the scientific community, unreliable or absent benefits seem equally likely to result, but if you don't try, you don't find out. None of this, of course, is a direct effort to repair the underlying causes of aging. Rather, it is a way to force damaged machinery back into action. As stem cell therapies demonstrate, that can nonetheless produce some degree of benefits, but the damage that causes aging is still there, and that limits the scope of those benefits.

Youthful Blood Reverses Menopause, Aging In Ongoing Clinical Trials

Preliminary results from the world's first clinical trials to reverse menopause and its associated negative health effects in women has shown reversal of menopausal symptoms and hormone restoration to fertile levels. Since July 2017, the California-based Inovium trials have been evaluating the link between a new treatment to restore ovarian function discovered in 2015 by partner clinicians in Athens, Greece. Approximately 10 women and their partners have been selected to move forward in the trial, which will further examine their progress as they begin In-Vitro Fertilization and other strategies for late-life pregnancy. Over 100 additional women have received the treatment in 2017, with over 75% of all women proceeding forward positively towards pregnancy.

The clinical results of the California trials have effectively reproduced the success of preclinical trials conducted in Greece in 2015, where Platelet Rich Plasma (PRP) injections were discovered to rejuvenate the ovaries of menopausal women, restore fertility, and pursue pregnancy. Of more than 60 women who received the treatment preclinically, over 75% now have the option of natural pregnancy or in vitro fertilization, including 9 successful pregnancies. Over 75% have also seen overall hormone levels return to youthful levels. No donor is needed - instead, the patient's own genetic material is used to heal the body. The basic process involves the removal of the patient's own blood plasma, enrichment via centrifuge, and re-injection into the ovaries once elements commonly present in youthful blood have emerged.

As a point of comparison, one might also read the following open access review of the ovarian stem cell niche and the factors leading to its decline with age. The authors argue that immune system and circulatory system function, both of which are certainly line items thought to be beneficially influenced in parabiosis studies, go some way towards determining ovarian function. You can join the dots here to see why research groups might think this is all worth a try, even if approaches intended to change the signaling environment in the bloodstream are really doing nothing to repair the well-described forms of cell and tissue damage that cause aging, and are thus limited in their outcomes.

Ovarian Stem Cell Nests in Reproduction and Ovarian Aging

The fixed primordial follicles pool theory, which monopolized reproductive medicine for more than one hundred years, has been broken by the discovery, successful isolation and establishment of ovarian stem cells. It has brought more hope than ever of increasing the size of primordial follicle pool, improving ovarian function and delaying ovarian senescence. The traditional view holds that stem cell aging contributes to the senility of body and organs. However, in the process of ovarian aging, the main factor leading to the decline of the reproductive function is the aging and degradation of ovarian stem cell nests, rather than the senescence of ovarian germ cells themselves.

Recent studies have found that the immune system and circulatory system are involved in the formation of ovarian germline stem cell niches, as well as regulating the proliferation and differentiation of ovarian germline stem cells through cellular and hormonal signals. Therefore, we can improve ovarian function and delay ovarian aging by improving the immune system and circulatory system, which will provide an updated program for the treatment of premature ovarian failure and infertility.

Comments

So it seems there are available stem cells in the ovary, which can be spurred into action with the right signals. Fascinating. The human body seems to have lots of stem cell niches that are almost completely inactive in an adult. I can only assume this is because the stem cells are kept so isolated and sealed off that a protective measure becomes a prison.

Posted by: Mark at November 1st, 2017 5:22 AM

Perhaps a 40% increase in life expectancy* is considered a 'limited outcome' in some circles, but for something that seem so imminently achievable, it might be worth pursuing, doncha think?

*(but in mice, of course)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773817/

Also, for those who think that 'The Change' itself is not such a big deal:
" I have already had one menopause. It was chemically induced five years ago as a treatment for my endometriosis ... I was given a course of injections of leuprorelin, ... it can block testosterone in men and oestrogen in women, hence it is used ... to chemically castrate paedophiles ..."
https://www.theguardian.com/society/2015/dec/15/what-science-doesnt-know-about-the-menopause-what-its-for-how-to-treat-it

Posted by: CD at November 4th, 2017 11:38 AM

CD: That's a 12% increase.

Posted by: Antonio at November 4th, 2017 5:00 PM

@CD: Gains of 40% in mice through adjustment of metabolism have effects probably smaller than 5 years in humans. We know this.

All of the methods with mouse and human data show this sort of relationship, and all of the methods tested to date are forms of metabolic tinkering that don't address the underlying causes of aging in the SENS model.

Senolytic studies in humans should be watched very closely, because here is the first repair-based approach to aging that is not metabolic tinkering. We have no idea how the mouse to human ratio of effects will turn out. One could argue either way.

Posted by: Reason at November 4th, 2017 5:28 PM

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