Extra ‘X’ Chromosome Helps Women Age Better

Even without this biological advantage, everyone, at any age, can take steps to improve their health, say experts on aging.

By Jerilyn Klein

Mortality records show women typically outlive men, and the benefits of having that extra X chromosome run much deeper and wider than many of us realize, according to experts on aging. But men shouldn’t fret. Both biologic sexes can improve their health and longevity by taking better care of their bodies and minds — even if they wait until their senior years.

“We mostly think of this as women having some sort of advantage later in life, but in fact they have the advantage of survival throughout life,” Steve Austad, PhD, chair and distinguished professor of the Department of Biology at University of Alabama, Birmingham, said during a recent webinar. Girls are also more likely than boys to survive to ages 1 and 5, said Austad, who has studied this data.

What’s also unique about women’s longer survival rates, which make them different than many other species, is that “it doesn’t seem to matter under what conditions they live,” he said. “This is one of the most robust features of human biology that we know.”

The pandemic has also illuminated biological sex differences on health. If men are infected with COVID-19, they’re more likely to be hospitalized; if hospitalized, they’re more likely to go to the ICU; and once they’re in the ICU, they’re more likely to be put on a respirator, said Austad. “They’re about twice as likely to die once they’ve gotten the disease.”

Austad is senior scientific director for the American Federation for Aging Research (AFAR), which hosted the webinar, “Sex Differences in Aging,” as part of its Living Better Longer series. Since its 1981 founding, AFAR has providing nearly $189 million to support more than 4,300 researchers studying the science of healthy aging at institutions around the world.

The webinar was moderated by Sarah Smith, editor-in-chief of Prevention magazine and Spencer Dukoff, deputy editor of Men’s Health magazine. Dena Dubal, MD, PhD, the chair of aging and neurodegenerative disease in the Department of Neurology at University of California, San Francisco, was the other expert speaker on the panel.

“In every single society that records mortality, from Sierra Leone to Japan, women live longer,” said Dubal, a two-time AFAR grantee. Female whales, lions and some of the mice she studies in her lab also have that advantage.

When asked what sparked her interest in sex differences in aging, she said her great-grandmother lived until nearly 90 — twice as long as her husband — in a rural town in India that was hit with epidemics and famine. Dubal’s great-grandfather — “he was a handsome, robust, amazing man” — died in his 40s.

Austad’s path to this discipline was less personal. Years ago, he read about mice who were treated with experimental drugs to see if this could make them live longer. (It only helped the males, he said). Around this time, he also read about the 1846-1847 Donner Party disaster; half the males and less than one-third of the females in this California-bound group of pioneers died during a winter trek through Sierra Nevada.

An Unconventional Experiment

Neither Austad nor Dubal know exactly how sex chromosomes and hormones contribute to longevity but they’re trying to find out. Having answers “may lead us to pathways of biology and medicine that could help us to live longer and better,” said Dubal. What she does already know, based on an unconventional genetic experiment her lab did with mice, is that sex chromosomes do contribute to lifespan, she said.

Her lab studied four different types of mice: Genetically female mice (XX chromosomes) with female gonads (ovaries); genetically female mice with male gonads (testes); genetically male mice (XY chromosomes) with testes; and genetically male mice with ovaries. Dubal and her colleagues found the genetically female mice lived longer, regardless of whether they had ovaries or testes.

Although women tend to be frailer than men who live well into old age, their minds are sharper, she said. This may be in part due to their greater likelihood to form social networks, she said. But it could also perhaps be rooted in biology.

“We now understand that there are more brain-related genes on an X chromosome than any of the other autosomes, or any other part of our genetic code,” she said.

It’s Not All Good in XX Territory

Dubal and Austad think that women’s seemingly stronger immune systems could be in part related to pregnancy. “Women have cells from other individuals floating around in their body,” noted Austad, including babies they gave birth to or miscarried. But both researchers acknowledge that women’s more responsive immune systems aren’t always a benefit despite offering some protection against infectious diseases.

“By being primed to trip so quickly, it’s like a smoke alarm that may go off when it shouldn’t, and you end up with these are autoimmune diseases,” said Austad.

For example, Dubal noted that women are more susceptible to contracting multiple sclerosis. Men, on the other hand, are more likely to contract Parkinson’s, another neurodegenerative disease. Dubal, who studies brain resiliency, also noted that the risk of getting Alzheimer’s disease is pretty similar for men and women up until age 80. After that, women have a higher risk. Among all people living today with Alzheimer’s two-thirds are women, she said — although part of that is that they live longer.

Additional Reading: Some Encouraging Signs on Dementia  

Austad also pointed to what is known as the mortality/morbidity paradox: Later in life, men, on average, are healthier than women. The burden of really severe, complicated health problems, multiple diseases and disabilities falls primarily on females, he said, “because, again the males grabbed their chest, they fell over 20 years earlier.”

“If we could figure out how to make men live as long as women, and we could make women stay as healthy as well, we’d be a long way into improving, enhancing and prolonging the quality of our lives,” said Austad.

Self Preservation

“Sex differences are more than just interesting,” said Dubal. “They may again lead the way to new treatments and medicine.”

The good news, say she and Austad, is that lifestyle changes can also help make a difference in how both men and women age.

“Our body and minds don’t live in isolation,” said Dubal. “I like to say what is good for the heart is good for the mind,” including exercise, diet, keeping stress low and having a social network.

It’s also never too late to adapt these lifestyle changes. “I don’t think anybody would have expected if you took up weightlifting when you’re 90 it was actually going to improve your strength, but it does,” said Austad. “To me, the thing that’s most exciting is that things that we start doing later in life, including taking new breakthrough drugs or other interventions that can have a major impact on our future health.”

Although he noted that no one has lived beyond 122½ years, he expects that to change in the foreseeable future.

“I have this famous wager with something about when the first 150-year-old person will be alive,” he said, “and my side of the wager is that that person is already alive.”

Jerilyn Klein is editorial director of Rethinking65.

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