The X Factor: Why Women May Be Healthier Than Men

The Reason Women Live Longer May Lie in Their Second X Chromosome

By Denise Mann
WebMD Health News

Reviewed By Laura J. Martin, MD

Sept. 28, 2011 -- “X” may really mark the spot when it comes to why women live about five to 10 years longer than men and are less likely to develop certain diseases.

Specifically, it's the X chromosome and the microRNA -- or tiny strains of ribonucleic acid -- that it contains. Men have one X chromosome and one Y chromosome, and women have two X's. Their microRNA tells our genes what to do or not to do.

Robert G. Lahita MD, PhD, explains it like this: “How does a daffodil know to bloom in the spring?  The microRNAs are in the chromosome for blooming and are temperature sensitive so as soon as the temperature gets to be in a certain range, the gene goes into effect largely because the microRNA tells it to,” he says. He is the chairman of the department of medicine at Newark Beth Israel Medical Center in New Jersey. “Voila, we have a bloom.”

Researchers from Ghent, Belgium, mapped out all of the microRNA found on the X chromosome in both humans and mice. They were able to highlight the microRNA that plays a role in our immune system's ability to ward off infections and cancer. Much of this microRNA is found on the X chromosome, which shows that the genetic deck may be stacked in women's favor.

The new study appears in BioEssays.

This research is still in its infancy, says study researcher Iris Pinheiro of the Flanders Institute for Biotechnology in Ghent. “The future will tell whether X-located microRNAs are indeed contributing to gender differences in what concerns to immune response and cancer onset.  But I have no doubt that this is so.”

Are Our Genes Our Destiny?

Is it all about the X? “I would not say that all is in the 'X,' but as a geneticist I would say that a lot is in the genes,” Pinheiro says. “At the end of the day we are a product of our genome, and in many cases we cannot escape detrimental mutations which cause certain diseases, even if we have a healthy lifestyle.

“We can shape their consequences, and we can postpone or dribble the symptoms,” she says in an email.  “It is still important to maintain a healthy lifestyle. We don't want to accelerate the process or end up with diseases for which we were not even predisposed to in the first place.”

“Women do live longer and may have fewer problems with certain infections diseases than men,” says David Pisetsky, MD, chief of rheumatology at Duke University Medical Center in Durham, N.C.

Some of the why may lie in the Y (chromosome), he says. “Women have two X and men only wind up with one,” he says. The genetic makeup of women is different from men because they have a backup X chromosome. “Maybe males get in trouble because they just have one X and no backup.”

One theory is that some genes on the X chromosome may be silenced or inactivated. This leaves men at a disadvantage because they only have one X. Pisetsky says that the extra X may be a buffer from what is defective or silenced on a single X chromosome.

Women may live longer and be less likely to develop some diseases, but they are at much higher risk for autoimmune diseases such as lupus and rheumatoid arthritis.

“It is a trade-off,” Pisetsky says.

Sex Hormones Also Contribute to Gender Differences

Other factors such as sex hormones including estrogen and progesterone and the environment may also play a role.

“Genetic differences definitely matter and there is ongoing interest and evidence that having one or two X chromosomes can impact ... differences between the sexes resulting in differential susceptibility to autoimmune diseases and even viral infections,” says Sabra L. Klein, PhD. Klein wrote an editorial that accompanied the new study. She is an assistant professor of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore.

“There is an equally compelling body of work to show that hormones, including testosterone and estrogens, impact the functioning of the immune system to alter development of disease,” Klein says via email.

“We like rules of thumb and simple stories and the ... differences between the sexes is anything but simple and likely involves both genes and hormones,” she says. “Many differences are hardwired in our genes, but the magnitude of these differences when faced with challenges may be affected by our hormonal environment.”

Many questions remain. “Can we therapeutically manipulate the expression of our genes or concentrations of hormones to reverse susceptibility to disease? Can information about gene expression and hormonal environment be used to tailor treatments differently for men and women? Do we have to treat men and women differently in order to treat them equally?”

Michael D. Lockshin, MD, has been talking about the X factor for years. He directs the Barbara Volcker Center for Women and Rheumatic Disease at Hospital for Special Surgery in New York City.

When asked if it all boils down to the X, he says, “Yes I think so.”

That said, environment also affects how long we live and what diseases we develop. “There is much more to look for in the environment,” he says in an email.


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SOURCES: Robert G. Lahita , MD, PhD, chairman, department of medicine, Newark Beth Israel Medical Center, Newark, N.J. Michael D. Lockshin, MD, director, Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, New York City. David Pisetsky, MD, chief of rheumatology, Duke University Medical Center, Durham, N.C. Pinheiro, I. Bioessays, 2011. Klein, S. Bioessays, 2011. Sabra L. Klein, PhD, assistant professor, molecular microbiology and immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore. © 2011 WebMD, LLC. All rights reserved.

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