By William J. Cromie
Studying people who live 100 years and more leads Harvard researchers to conclude that menopause is a major determinant of the life spans of both women and men.
Women's life span depends on the balance of two forces, according to Thomas Perls, a geriatrician at Harvard Medical School. One is the evolutionary drive to pass on her genes, the other is the need to stay healthy enough to rear as many children as possible. "Menopause draws the line between the two," Perls says. It protects older women from the risks of bearing children late in life, and lets them live long enough to take care of their children and grandchildren.
As for men, Perls believes "their purpose is simply to carry genes that ensure longevity and pass them on to their daughters. Thus, female longevity becomes the force that determines the natural life span of both men and women."
"Most animals do not undergo menopause," adds Ruth Fretts, an obstetrician-gynecologist at Harvard-affiliated Beth Israel Deaconess Medical Center in Boston. "It seems that menopause evolved in part as a response to the amount of time that the young remain dependent on adults to ensure their survival."
Pilot whales, for example, suckle their young until age 14, and they, along with humans, are two of the few species that menstruate.
Human females eventually become so frail that bearing children involves a high risk of death. Earlier in evolution, that was as young as 35 to 40 years old. "Anyone who developed a genetic alteration that caused infertility, i.e., menopause, obtained a survival advantage over females who continued to be fertile and died bearing children," Perls says.
The Gender Gap
This reasoning, however, does not explain why women live so much longer than men. "In all developed countries and most undeveloped ones, women outlive men, sometimes by a margin of 10 years," Perls and Fretts note. "In the U.S., average life expectancy at birth is about 79 years for women and about 72 years for men."
The gender gap is most pronounced in those who live 100 years or more. Among centenarians worldwide, women outnumber males nine to one. Perls and Fretts are studying all centenarians from eight cities and towns around Boston, 100 people in all. Eighty-five are women.
The mortality gap varies during other stages of life. Between ages 15 and 24 years, men are four to five times more likely to die than women. This time frame coincides with the onset of puberty and an increase in reckless and violent behavior in males. Researchers refer to it as a "testosterone storm." Most deaths in this male group come from motor vehicle accidents, followed by homicide, suicide, cancer, and drownings.
After age 24, the difference between male and female mortality narrows until late middle age. In the 55- to 64-year-old range, more men than women die, due mainly to heart disease, suicide, car accidents, and illnesses related to smoking and alcohol use. Heart disease kills five of every 1,000 men in this age group.
"It seems likely that women have been outliving men for centuries and perhaps longer," say Perls and Fretts. Even with the sizable risk conferred by childbirth, women have outsurvived men at least since the 1500s. Although, in the United States between 1900 and the 1930s, the death risk for women of childbearing age was as high as that for men. Since then, improved health care, particularly in childbirth, has put women ahead of men again in the survival struggle, as well as raising life expectancy for both sexes.
A longer life doesn't necessarily mean a healthier life, however. While men succumb to fatal illnesses like heart disease, stroke, and cancer, women live on with non-fatal conditions such as arthritis, osteoporosis, and diabetes. "While men die from their diseases, women live with them," Perls comments.
One contributor to the gender difference in life span is the influence of sex hormones. The male hormone testosterone not only increases aggressive and competitive behavior in young men, it increases levels of harmful cholesterol (low-density lipoprotein), raising a male's chances of getting heart disease or stroke.
On the other hand, the female hormone estrogen lowers harmful cholesterol and raises "good" cholesterol (high-density lipoprotein). Emerging evidence suggests estrogen treatment after menopause reduces the risk of dying from heart disease and stroke, as well as of dying in general.
Perls and Fretts believe that longer life means survival of the fittest, and women, evolutionarily speaking, are more fit than men. The longer a woman lives and the more slowly she ages, the more offspring she can produce and rear to adulthood. Therefore, evolution would naturally select the genes of such women over those who die young.
Long-lived men would also have an evolutionary advantage over their shorter-lived brethren. However, says Perls, "studies of chimps, gorillas, and other species closely related to humans suggest that a male's reproductive capacity is actually limited more by access to females than by life span. And because men have not been involved in child care as much as females, survival of a man's offspring, and thus his genes, depended not so much on how long he lived, but on how long the mother of his children lived."
In their studies of centenarians, Perls and Fretts found that a surprising number of women who lived to be 100 or more gave birth in their forties. These 100-year-old women were four times as likely to have given birth in their forties as women born in the same year who died at age 73. A study of centenarians in Europe by the Max Planck Institute of Demography in Germany found the same relationship between longevity and fecundity.
This does not mean that having a child in middle age makes a woman live longer. Rather, Perls says, "the factors that allow certain older women to bear children -- a slow rate of aging and decreased susceptibility to disease -- also improve a woman's chances of living a long time. Extending that idea, we argue that the driving force of human life span is maximizing the time during which woman can bear children. The age at which menopause eliminates the threat of female survival by ending further reproduction may therefore be the determinant of subsequent life span."
Closing the Gap
If this is true, then the genes of female centenarians hold the secrets of a longer, healthier life. And these are no ordinary genes. Whether the average person drinks, smokes, exercises, or eats her vegetables adds or subtracts five to ten years to or from her life. But to live an additional 30 years requires the kind of genes that slow down aging and reduce susceptibility to conditions such as Alzheimer's disease, stroke, heart disease, and cancer.
Clues about what those genes are and how they work could come from studying those who survive 100 years or more, Perls believes. The New England Centenarian Study he runs is the only scientific investigation of the oldest oldsters being done in the United States. He has now expanded it to include all centenarians in the city of Boston, about 100 more people.
"We think that centenarians are a tremendous resource for the discovery of genes responsible for aging and the ways in which aging occurs," says Perls. "Finding these genes could lead to testing people and determining who might be disposed to accelerated aging via diseases such as Alzheimer's, cancer, heart disease, and stroke. Such individuals might eventually be treated to extend the prospect of their living longer."
The oldest person for which reliable records exist was a woman who recently died in France at the age of 123. "Reaching such an age is like winning the lottery," Perls comments. "The odds are about one in 6 billion. From a practical point of view, we can consider 100 years as the average maximum of human life. We're not there yet, of course. At present, average life expectancy for those born after 1960 is about 85 years."
Although women can expect to live longer than men, the gap is closing. Death rates have begun to converge in the past 20 years. Some researchers attribute the convergence to women taking on the behaviors and stresses formerly considered the domain of males -- smoking, drinking, and working outside the home.
For example, Perls and Fretts point out that deaths from lung cancer have almost tripled in women in the past 20 years. One study concluded that, on average, middle-aged female smokers live no longer than male smokers.
"Smoking," Perls and Fretts conclude, "seems to be the 'great equalizer.'"
Copyright 1998 President and Fellows of Harvard College