Why sex bias in labs means women are the losers in aging research

IExtending human lifespan is a multibillion-dollar industry and is hailed as the most fascinating scientific challenge in modern history. But if a drug is ever discovered to extend lifespan, one thing seems certain: it is highly unlikely to work in women – and almost unthinkable that it will work in mothers.

That’s because, experts say, cages in laboratories around the world are filled with white mice that share a striking similarity: They’re all male.

This is a serious problem, says Dr. Steven Austad, biologist and author of the bestselling Methuselah’s Zoobecause the sex differences between rodents are significant – and the differences between virgin female mice and mice that have already given birth are even greater.

By ignoring those differences, Austad said, he said it was “almost improbable” that a drug tested only in male mice would also work in female mice. It was “more or less a complete coincidence” if it also worked in women who had given birth.

“It’s a huge problem,” he said. “The lack of rigorous research in female mice means we only know what works in male mice, to the complete exclusion of female mice.”

About 75% of the drugs that extend the lifespan of mice only work in male mice. The drugs were developed in male mice and then tested on both sexes. It turned out that the females did not respond.

Although researchers know that female mice respond differently to drugs than male mice, no studies have yet been done on individual interventions that could help women live healthier, longer lives.

A sobering example is from 1993, when the first articles on low methionine diets were published. The results were astonishing: the diet extended the lives of rats by more than 40%. Several follow-up studies were conducted in the 1990s, all of which showed the same astonishing results.

It took 12 years before it was pointed out that the rats in each study were exclusively male, and that it might be a good idea to test on females as well. When the study was repeated with females, it turned out that the life-giving diet for males caused some of the females to die prematurely.

Jennifer Garrison, an assistant professor specializing in reproductive health and ovarian aging at the Buck Institute for Research on Aging, said there is “a really pervasive sexual bias in biomedical research and in clinical research that goes back as far as we’ve had biomedical research. The male body has been the foundation of biology for the last 100 years, and if you don’t study the female body, you’re never going to learn anything about it.”

Garrison criticized nearly all of the lifespan studies for failing women. She argued that even the few studies that used virgin female mice ignored the period in which the mice were in their reproductive cycle.

“You absolutely have to be aware of this because women’s physiology is so different throughout their cycle,” she said. “If you don’t monitor where they are in their cycle, it’s like having a blindfold on.”

Another problem with lifespan research, she said, was that in the extremely rare cases where female mice had been properly studied, it was specifically stated that they had never given birth, ignoring the multiple and lasting effects that childbirth had on the females’ physiology.

According to an article by Austad, which will soon be published in the magazine Limits of growing oldOne of the reasons why more progress hasn’t been made in extending women’s healthy lifespans is that researchers aren’t interested in studying the issue.

“It’s so striking that we need to look at it more deeply, but no one pays attention to it and it keeps happening,” said Austad, founder and director of the Nathan Shock Center of Excellence in the Basic Biology of Aging at the University of Alabama at Birmingham.

“There was a large study that came out very recently and did what most studies do: it showed an experiment with mostly male mice, then it hid a quick glance at females deep in the fine print, and then it combined both sexes in the results. There was never a glance or mention that there might or might not be a sex difference.”

He said more time should be spent trying to understand these sex differences “so we can develop medicines that benefit both sexes. Women deserve to be taken seriously. Science really needs to change to honor that.”

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