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I would like to use CRISPr Cas9 technology to extend the life expectancy of my fictional civilizations. From what I understand, CRISPr could extend life by lengthening telomeres and improve quality of life by editing damaged DNA, perhaps even enhancing it. This does not look like it would change the time humans would enter puberty (12 - 14 years old and lasting another 5 to 8 years approximately).

My concern is that female ova do not last very long. Within 24 hours of ovulation, ova die if not fertilized, and thousands more die before that they even reach ovulation. This limits a woman's fertile period because she will run out of eggs and stop producing estrogen, triggering menopause.

My question is: Is there a biological/genetic alteration that can be made to female humans of these civilizations to extend their fertility period without changing the age at which puberty will occur?

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  • $\begingroup$ Puberty starts earlier in contemporary humans than 200 years ago. Apparently, menopause also starts later. However, we do not have much data on menopause due to the insufficient records and short lifespans. If you are extending life by 100-200 years, you might not need any changes in the reproduction system at all. $\endgroup$ – Olga Nov 2 '17 at 1:26
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    $\begingroup$ Women do not actually run out of ova, that has been refuted by recent work. ejmanager.com/mnstemps/2/2-1295498802.pdf and sciencedirect.com/science/article/pii/S0015028213032627 they keep making new ova until menopause menopasue is not triggered by running out of ova, the number is not set at birth as was previously believed. All you have to do is delay menopause to increase the fertile period. $\endgroup$ – John Nov 2 '17 at 15:56
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Your question is based on outdated information. Women do not actually run out of ova, that has been refuted by recent work. ejmanager.com/mnstemps/2/2-1295498802.pdf and sciencedirect.com/science/article/pii/S0015028213032627 .

Menopause is not triggered by running out of ova, menopause is defined as when the body stops producing ova. There is an important distinction, both are triggered by a sudden drop in estrogen one does not cause the other.

Nor is the number of ova set at birth as was previously believed, mammals keep making new ova from stem cells until menopause contrary to what was previously believed.

All you have to do is delay the drop in estrogen production to increase the fertile period.

If you want to make them more fertile during their monthly cycle, change men so their sperm can survive longer like other animals, sperm can sit inside the woman for a few days waiting for an ova and still be viable just increase how long it can do so.

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  • $\begingroup$ Very interesting articles. I wasn't aware of this new theory of neo-oogenesis, but I think it's worth mentioning that this idea is still highly controversial. Your own sources acknowledge that the field is very much divided on the existence of Germinal Stem Cells in the adult ovary and whether or not they are responsible for continued production of oocytes. Certainly, a worthwhile theory to bring up, but the certitude with which you presented it is unwarranted. $\endgroup$ – Mike Nichols Nov 2 '17 at 16:27
  • $\begingroup$ Highly controversial or disproven; see end of review article. $\endgroup$ – Willk Nov 2 '17 at 20:26
  • $\begingroup$ Controversial in humans certainly disproved not al all. ncbi.nlm.nih.gov/pmc/articles/PMC3939264 the main issue is that difintive proof one way or the other would require an unethical experiment in humans (manipilation of the "host" genome), in mice that is not really an issue. The most common method utilized searching for markers in problematic because we don't know if the markers would be consistent or constant. $\endgroup$ – John Nov 3 '17 at 3:12
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I think anyone right now using CRISPr to achieve this would be blundering in the dark. It is not understood why oocytes die. The mechanisms behind the death are unclear. It might be adaptive some how that they die - the "nurse cell" hypothesis.

Yuan-Chao Sun et alThe role of germ cell loss during primordial follicle assembly: a review of current advances. Int J Biol Sci. 2017; 13(4): 449–457.

The mechanism or cause of this oocyte loss remains largely unknown. There is no evidence that only one factor or pathway can explain the entire germ cell loss in the fetal ovary. It is well accepted that PCD can be triggered by all kinds of intra and extracellular stresses including DNA damage, hypoxia, or growth factor withdrawal. Currently three hypotheses have been proposed to explain germ cell loss during this process.

She goes on to lay out the three hypothesis which get pretty technical, but the third involves the dying oocytes donating their nutrients to those that survive.

I would also point out that playing with programmed cell death in germ cells may be playing with fire. Germ cells can give rise to cancer and in some ways it is surprising this does not happen more often. The mechanisms which cause oocyte loss over life might also be protective against cells that develop mutations.


There is a fine and straightforward method by which women can extend their fertility period.

1: Bank oocytes. Freeze them away.
2: Later, use these oocytes for in vitro fertilization, with hormonal replacement if postmenopausal.

This has been successful in women up to and over age 50 although

As women approach and exceed 50 yrs of age, complications such as increased hospitalisation, pregnancy-induced hypertension, GDM and lower birth-weight babies begin to surface .

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2788687/

That sounds a lot safer to me than editing the genome!

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There's a few different answers you could try for this, ordered loosely by degree of genetic alteration needed. As far as I'm aware, none of these would be directly connected to the age at which puberty begins, although the later ideas might have odd side effects. A warning: I'm not a geneticist, so I can't tell you exactly what genes would have to be modified to do this.

Produce more viable eggs

This one is fairly simple. Female humans (I don't know if this is true for other mammals, but it probably is) are born with a finite number of ova, perhaps a few thousand. A lot of these are lost in the early years, until at puberty the typical woman has a few hundred viable eggs. At one a month, this will last for a couple of decades.

If you can tamper with the genetics a little, causing female babies to be born with more eggs and/or making a larger percentage of them turn out to be viable (which might call for larger ovaries, but don't take my word on that), you can extend the childbearing period, at least in theory. It won't cover an infinite number of years, but I'm not under the impression you're looking for outright immortality. This may also require tampering with the mechanism that causes menopause, since I'm pretty sure that running out of eggs is not the only factor.

Modify the ovaries to produce eggs continuously, much like sperm

This one is self-explanatory; if women keep making eggs, they won't run out. This is the only solution (out of my list) that would work on the scale of thousands of years; the others would eventually fail if a woman had a few hundred children (by which point many would probably have perished of childbirth-related complications, but that's not really relevant here). There are potential side effects (older men generally have lower-quality sperm, I think due to DNA replication errors mounting up over time), so keep that in mind. Again, you'll have to make sure menopause isn't triggered by other means.

Change the reproductive cycle

Now we're getting into serious genetic modifications; this might be outside the scope of changes you're willing to run with. There's a couple of different paths to go with this, but the basic idea is to cut down on wasted ova by reducing or eliminating cases where an ova is released without being fertilized.

Induced ovulation, such as what is seen in cats (basically, sex causes them to ovulate), is one possible solution. I hope it's obvious why this would result in a much higher percentage of released ova being fertilized and (barring miscarriage, stillbirth, etc.) resulting in children.

There's also the idea of making ova linger for more than a day or two after being released. This would require some notable biology changes, since the woman's body would have to remain capable of nurturing a fertilized embryo; you'd have to avoid menstruation for much longer.

Pushed to the logical extreme (the embryo lingers until fertilized), you'd have women who were either pregnant or fertile at all times after puberty, and who had no periods at all. There's a reason why this doesn't happen in nature: maintaining a fertile state in females requires lots of blood-rich tissues in the uterus and is very energy-expensive, to the point where shedding it regularly and regrowing it a few weeks later (periods) is significantly more efficient than simply maintaining it continuously. Women would end up eating a lot more.

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  • $\begingroup$ Induced ovulation would only work if women only had sex when they wanted children. $\endgroup$ – Real Subtle Nov 2 '17 at 12:04
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    $\begingroup$ Another option is to increase the length of the menstrual cycle. If women came into estrus only once or twice a year, you wouldn't run out of eggs, and I'm sure most women would not be unhappy about the reduced frequency. $\endgroup$ – Sherwood Botsford Nov 2 '17 at 13:46
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    $\begingroup$ @RealSubtle That's entirely true. I never said these solutions were without side effects. That one in particular could result in some interesting directions for a story as people deal with those effects. $\endgroup$ – Palarran Nov 2 '17 at 16:20
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I think it’s a fairly safe bet that extending life expectancy by gene-editing is a more difficult task than delaying the onset of menopause. Not that we know exactly how we might go about either at the moment, but the multitude of issues that crop up as we age throughout our bodies that would need to be solved for a significant increase in longevity absolutely dwarf in complexity the relatively simple desire to maintain the ovarian supply of eggs for longer. At birth the human ovary contains around 1 million oocytes which have the potential to become eggs, but only about 500 of these oocytes will ever actually ovulate. The remaining 99.9% of oocytes die before they ever get a chance. Menopause begins when ovaries run out of oocytes. All we would need to do to delay menopause is slightly decrease the rate at which oocytes are wasted, from the aforementioned 99.9% to just 99%, and we’ll have enough oocytes to last a millenia. It’s possible that a fairly simple hormonal shift could produce this effect.

If your society has the technology to extend the useful lifespan of every other organ in the body it’s likely that preventing menopause is a trivial problem.

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CRISPr is largely irrelevant information in this question

The amount of eggs a woman has is currently a finite thing however the number, the frequency, and productive age limit are currently variable.

One woman managed to give birth as late as in her 70's.

So your question: is there a biological alteration that can be done? yes you could GE everyone to have the traits that allowed her to be capable of this. Or simply you could selectively breed your population such that females are only allowed to reproduce at certain progressive ages each generation. This would naturally increase the proliferation of said adaptations.

This would also be an avenue into increasing the natural lifespan of human beings without CRISPr.

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Robert Heinlein novel, Time Enough for Love, introduced the idea of the Howard families, people who have been selectively bred for longevity.

Whilst it doesn't exactly match the question you asked it is an alternative method of genetic manipulation that does not carry the risks of genetic modification.

A civilisation that want to increase the longevity of it's population could easily follow this method with only a few cultural changes, removing the stigma for women who have children with multiple men or out of wedlock for example as they are improving the stock of the race by doing so.

Increased benefits for children who are born to such unions, free education and health care etc.

For a glimpse of what the darker side of such a civilisation could look like, watch Gattaca where those deemed genetically inferior had less opportunities in life.

Just an alternative for your consideration.

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YES there is a really easy, already employed way: freeze the eggs. That's literally it. Then in-vitro fertilze them (not 100% necessary afaik) and implant them back in the mother. Since they are cryogenically frozen, they (and thereby the mother) are fertile forever.

The only problem that comes to mind is that after menopause the female body may have problems with embryos inside it (but that's just speculation, I have no idea whether that is actually the case).

Another problem that old women have nowadays is that birth complications and some complications for/in the child are FAR more common with older mothers, but since they stay "young" (by most standards) due to the treatment, I would deem these problems of our time, not the future you are crafting

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