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Feb 28, 2019

Can We Turn Back Time on Women’s Biological Clocks?

New research initiatives in human longevity offer a chance to extend female reproductive years.

No matter how good a day we’re having, our decisions are always in one way or another influenced by our biological lifespan clocks. How we spend our leisure time or invest our money is often determined by our physical health and how long we think we have to live. Women must also track a second biological clock, and the race against reproductive senescence, otherwise known as menopause, is a pressing issue for many. The impact of the reproductive clock on the decisions women make can be profound.

A global effort to increase healthy human longevity is now underway. However, increasing lifespan without also solving female reproductive senescence will only increase the growing reproductive divide between men and women: Men retain reproductive capacity into their golden years while women typically lose theirs entirely around the fifth decade of life.

This asymmetry forces women to make difficult compromises on important decisions around education, jobs, marriage and family. The social, emotional and economic costs of these compromises to women, and thus to society, are incalculable. The time has come for science to help address this growing inequity.

What is the biological basis of this reproductive asymmetry? Scientific theories in this area are surprisingly fallow. For more than a century, the idea that the number of eggs a woman has gradually declines throughout adult life has remained the consensus dogma of reproductive biology.

The intellectual lineage of this thinking is brief. German anatomist Wilhelm Waldeyer, a brilliant essayist who coined the words “neuron” and “chromosome,” also fathered a theory in 1870 that egg production ceases at a woman’s birth. In 1951, British zoologist Solly Zuckerman further proposed that women have a fixed reserve pool of oocytes, the cells that eventually become eggs, before birth. The notion of a biologic clock for women’s fertility was born.

I first became curious about the subject of female reproductive senescence during an independent study class I took with professor E.O. Wilson while studying at Harvard. I wondered why there hadn’t been evolutionary selection toward sustained female reproductive capacity or at least deferral of menopause. The prevailing argument has been that for most of human evolutionary history, survivorship declined so rapidly with age that beneficial traits that emerge during older years, such as the extension of reproductive years, would have negligible impact on selection. However, over large time scales even small advantages should have precipitated self-reinforcing runaway evolution toward lengthening female reproductive capacity. The contradiction between these views intrigued me.

One explanation for the lack of runaway menopause deferral is the one advanced by Waldeyer and Zuckerman: Women simply run out of eggs. On the other hand, this view does not easily reconcile with the reality that spermatogenic capacity in men, though declining, persists into their dotage despite producing far most gametes (sperm) than women. Furthermore, menopause is almost never observed in other species. Perhaps reproductive senescence would eventually emerge for men or females in other species if they lived long enough, but we simply don’t know.

Here is a more radical explanation for the lack of runaway menopause deferral during evolution: Reproductive senescence is a trait favored by evolution from a multilevel selection perspective, an approach to understanding evolution from multiple points of view including genes, individuals and groups. As with the programmed senescence theory, programmed menopause theory has plenty of detractors who would argue that selfish interests of individuals would have induced mutations to edit out any such programs over our evolutionary history.

We could debate forever about the relative arguments for or against these and other explanations as to why menopause exists. However, as mentioned earlier, all women are racing against this clock regardless of its evolutionary origins.

Instead, I prefer using a philosophical approach modeled after Pascal’s Wager. One can’t prove that reproductive senescence is inevitable or biologically programmed. So I’m simply going to assume that reproductive senescence is programmed given the asymmetric payoff of that corner case. That is, if menopause is a program, it has a better chance of being reprogrammed—and thus solved—than if we failed to look for the existence of such programs because we assumed menopause was inevitable.

I’d like to first address a common concern that comes up in discussing both general human longevity and female reproductive longevity: Will success in these areas promote overpopulation and exacerbate stress on our resources and infrastructure? While fears about demographic expansion, which date to Benjamin Franklin and Thomas Malthus, remain in the public consciousness, I believe that the overpopulation thesis is overblown. The empirical data suggests that healthy longevity of a population is associated with the fall of the fertility rate below the replacement rate. If anything, demographic contraction may be a greater threat to our long-term future even if we are able to extend human lifespans and reproductive clocks.

The good news is, there are early signs that extending female reproductive years may be possible. On March 6, 2017, I hosted various leaders, including Nobel laureate Dr. Liz Blackburn and Dr. Eric Verdin, CEO of Buck Institute for Research on Aging, at San Francisco’s Exploratorium to discuss the future of human longevity. One of the speakers was Nicole Shanahan, founder and CEO of patent management company ClearAccessIP, who described her passion for reimagining longevity equality, including better equality between the genders. That led to numerous follow up discussions, and we received valuable input from Dr. Peter Ellison, Dr. Linda Giudice, Dr. Jonathan Tilly and others about the topic of reproductive senescence. The bottom line was that the scientific field needed a jump start.

It came rather quickly and in a big way: Shanahan just launched the Buck Institute’s new Center for Female Reproductive Longevity and Equality with a $6 million gift through her allocation from the Sergey Brin Family Foundation. The world may look back at this as a historic moment. Those of us in the field are hopeful that the eventual benefits of the growing longevity movement will accrue to everyone. Solving the divide of reproductive longevity between men and women would be a great start.

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