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'X' Factor Boosts Women's Health Longevity

Two X chromosomes put females at an advantage, expert says

TUESDAY, March 21, 2006 (HealthDay News) -- When it comes to the battle of the sexes, nature hands women extra ammunition right from the start.

The reason, according to geneticists: Females are gifted with two copies of the powerful X chromosome, while males are born with only one X, plus the relatively weak Y chromosome.

Genetics research is increasingly showing that, besides marking the DNA border between boys and girls, this divide gives women a decided advantage in warding off disease and increasing longevity.

"Even in utero, more males die than females. More males die with certain chromosomal abnormalities than females -- they die earlier, and they certainly are more vulnerable," explained Dr. Barbara Migeon, a professor in the Institute of Genetic Medicine at Johns Hopkins University School of Medicine in Baltimore.

She authored a special article outlining the "X advantage" in the March 22 issue of the Journal of the American Medical Association, which is devoted to issues of women's health.

Census takers have long noticed that women have a decided survival edge over men. According to 2003 federal data, American females live 80.1 years, on average, compared to 74.8 years for males.

"But, whenever I've read about things that might be responsible for these sex differences, it's always been limited to male-female differences in life experiences, or hormones, or reproductive apparatus," Migeon said. What's been left out, she said, is this fundamental genetic difference between the sexes.

That difference originates in the fact that women come with two copies of the powerful X chromosome, she said.

"People think the X is only about sex," Migeon said, "but it has 1,100 genes that do all kinds of things, from being involved in blood clotting to muscle function, to getting rid of [cellular] waste products. It's a very active chromosome."

Girls receive an X from each parent, while boys receive one X plus a comparatively "weak" chromosome, Y, whose small amount of active DNA is mainly concerned with the development of male characteristics.

Like all genetic material, the genes in the X chromosome can be mutated or dysfunctional, perhaps giving rise to disease.

"So, if there is a mutation on the X chromosome, the male has no good copy of the gene -- he's stuck with just this defect copy," Migeon pointed out. "However, females, having two X chromosomes, have the defective copy, but they may also have a normal copy on the other X chromosome. Essentially, they have a 'back-up.'"

This simple fact may explain why women appear to be more resilient against certain diseases, and early death, than males, she said.

But there's an added complication, something geneticists call "mosaicism."

Mosaicism refers to the fact that simultaneous expression of both copies of the X chromosome genes is lethal to cells. So, in any given woman's cells, one of her X chromosomes is switched off, while the other remains active.

"In that sense, I [and all women] am a 'mosaic' with respect to whether my mother's genes are functioning in my cells, or my father's genes," Migeon explained. Cell to cell, tissue to tissue, women's DNA is simply more varied in this respect than men's.

"Generally, mosaicism is an advantage," Migeon said, since it gives a woman's cells more flexibility if and when dangerous mutations arise.

But in rare cases, this advantage may backfire, she added. For example, doctors have long noticed that women are much more prone to autoimmune diseases -- illnesses such as scleroderma or lupus, where the body attacks its own tissues -- than men.

Migeon suspects that early in embryonic development, a small percentage of human females may develop a serious imbalance in the tug-of-war of gene expression between the two Xs, with one side clearly winning. This could influence key processes such as "self-recognition," where the developing immune system learns what cells and tissues are part of the self, and which are "foreign" and need to be attacked.

If self-recognition goes awry, autoimmune diseases that can plague the body for a lifetime may be the result, Migeon theorizes.

The "X factor" may even have broader implications. Studies in monkeys have suggested it may explain male/female differences in comprehending color, Migeon said. There's also evidence that X-based genetics influence everything from attention span (girls tend to be more attentive to tasks than boys) to personality traits, such as sense of humor.

According to Migeon, the X chromosome has languished in the shadows too long in discussions of health and behavioral differences between the genders.

"I've always felt that the public really needed to know more about it, and that physicians needed to think of it more, too," she said.

More information

For more on the interplay of genetics and health, visit the U.S. National Human Genome Research Institute.

SOURCES: Barbara Migeon, M.D., professor, Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore; March 22, 2006, Journal of the American Medical Association
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