Saturday, June 18, 2016

Real Deal #22: Why Women Live Longer than Men, But the Mystery Continues

129-year-old Antisa Khvichava

THE INTRODUCTION

Phys.org:
Women live longer than men. This simple statement holds a tantalizing riddle that Steven Austad, Ph.D., and Kathleen Fischer, Ph.D., of the University of Alabama at Birmingham explore in a perspective piece published in Cell Metabolism on June 14.

"Humans are the only species in which one sex is known to have a ubiquitous survival advantage," the UAB researchers write in their research review covering a multitude of species. "Indeed, the sex difference in longevity may be one of the most robust features of human biology."

Though other species, from roundworms and fruit flies to a spectrum of mammals, show lifespan differences that may favor one sex in certain studies, contradictory studies with different diets, mating patterns or environmental conditions often flip that advantage to the other sex. With humans, however, it appears to be all females all the time.

"We don't know why women live longer," said Austad, distinguished professor and chair of the UAB Department of Biology in the UAB College of Arts and Sciences. "It's amazing that it hasn't become a stronger focus of research in human biology."

Shape:
According to the latest U.S. report, life expectancy for the ladies is 81.2 years compared to 76.4 years for males (sorry, guys!). But even though the fact that women outliving men has become widely accepted as the norm, a new study led by University of California, Los Angeles and University of Southern California researchers shows that this difference in survival rate is actually a relatively recent phenomenon, beginning just in the 20th century.

"As infectious disease prevention, improved diets, and other positive health behaviors were adopted by people born during the 1800s and early 1900s, death rates plummeted, but women began reaping the longevity benefits at a much faster rate," the press release explained.

The biggest culprit for this surge of death rates for men? Heart disease, the study concludes. Even after accounting for deaths due to smoking, cardiovascular disease appears to still be the leading cause of most preventable deaths in men over 40.

That other reason? Lifestyle. The increasing rates of cardiovascular disease in men is attributed to health-related behaviors, in particular smoking and a diet high in both calories and saturated fats, says Beltrán-Sánchez. While there is little evidence of biology's role in this mortality gap between the sexes, there is still a possibility that men may experience an inherent, biological vulnerability to cardiovascular disease, he adds. 

Newsweek:
In relatively prosperous Western Europe, the average male lifespan is between three (UK) and six years (Austria, Spain, Greece) shorter than women’s. The gap gets even wider in Eastern Europe, where World Health Organisation figures show that Romanian and Polish men die seven to eight years before their female counterparts, while in Belarus, Russia and Lithuania, that figure stretches to 12 years (men go at 63, women at 75).

Even in countries with the highest male longevity rates (Canada, Cyprus, Israel and Japan, where men can expect to live to 80), women still come out on top, living to an average of 82 (84 in Japan) The question is: why? And the answer is that no one has the definitive answer.

“It’s just the way things are,” says a spokesman for the UK Department of Health.

THE EVIDENCE


Evidence of the longer lifespans for women includes:
  • The Human Mortality Database, which has complete lifespan tables for men and women from 38 countries that go back as far as 1751 for Sweden and 1816 for France. "Given this high data quality, it is impressive that for all 38 countries for every year in the database, female life expectancy at birth exceeds male life expectancy," write Austad and Fischer, a research assistant professor of biology.
  • A lifelong advantage. Longer female survival expectancy is seen across the lifespan, at early life (birth to 5 years old) and at age 50. It is also seen at the end of life, where Gerontology Research Group data for the oldest of the old show that women make up 90 percent of the supercentenarians, those who live to 110 years of age or longer.
  • The birth cohorts from the mid-1800s to the early 1900s for Iceland. This small, genetically homogenous country—which was beset by catastrophes such as famine, flooding, volcanic eruptions and disease epidemics—provides a particularly vivid example of female survival, Austad and Fischer say. Over that time, "life expectancy at birth fell to as low as 21 years during catastrophes and rose to as high as 69 years during good times," they write. "Yet in every year, regardless of food availability or pestilence, women at the beginning of life and near its end survived better than men."
  • Resistance to most of the major causes of death. "Of the 15 top causes of death in the United States in 2013, women died at a lower age-adjusted rate of 13 of them, including all of the top six causes," they write. "For one cause, stroke, there was no sex bias, and for one other, Alzheimer's disease, women were more at risk."
Cell Metabolism invited Austad to contribute this perspective paper, "Sex differences in lifespan."

Austad first became interested in the topic when Georgetown University asked him to lecture on it in 2003. Although lab models like the roundworm C. elegans, the fruit fly Drosophila melanogaster and the mouse Mus musculus are intensively used in scientific studies, people in those fields are not very aware of how longevity patterns by sex can vary according to genetic backgrounds, or by differences in diet, housing or mating conditions, Austad says.

Those uncontrolled variables lead to different results in longevity research. A survey of 118 studies of laboratory mice by Austad and colleagues in 2011 found that 65 studies reported that males outlived females, 51 found that females outlived males, and two showed no sex difference.

But if variables are carefully controlled, mice may prove to be a useful model to study sex differences in the cellular and molecular physiology of aging, Austad and Fischer write.

This understanding will be helpful as researchers start to develop drugs for human use that affect aging, Austad says. "We may be able to develop better approaches," he said. "There is some complicated biology underlying sex differences that we need to work on."

Differences may be due to hormones, perhaps as early as the surge in testosterone during male sexual differentiation in the uterus. Longevity may also relate to immune system differences, responses to oxidative stress, mitochondrial fitness or even the fact that men have one X chromosome (and one Y), while women have two X chromosomes. 

But the female advantage has a thorn.

"One of the most puzzling aspects of human sex difference biology," write Austad and Fischer, "something that has no known equivalent in other species, is that for all their robustness relative to men in terms of survival, women on average appear to be in poorer health than men through adult life."

This higher prevalence of physical limitations in later life is seen not only in Western societies, they say, but also for women in Bangladesh, China, Egypt, Guatemala, India, Indonesia, Jamaica, Malaysia, Mexico, the Philippines, Thailand and Tunisia.

One intriguing explanation for this mortality-morbidity paradox is a possible connection with health problems that appear in later life. Women are more prone to joint and bone problems, such as osteoarthritis, osteoporosis and back pain, than are men. Back and joint pain tends to be more severe in women, and this could mean chronic sleep deprivation and stress. Thus, the sex differences in morbidity could be due to connective tissue maladies in women, and connective tissue in humans is known to respond to female sex hormones.

But this is just one of several plausible hypotheses for the mystery of why women live longer, on average, than men.

BBC:
But the fact is that female chimpanzees, gorillas, orangutans, and gibbons also consistently outlive the males of the group, and you do not see apes – male or female – with cigarettes hanging out of their mouths and beer glasses in their hands.

There are many potential mechanisms – starting with the bundles of DNA known as chromosomes within each cell. Chromosomes come in pairs, and whereas women have two X chromosomes, men have an X and a Y chromosome. That difference may subtly alter the way that cells age. Having two X chromosomes, women keep double copies of every gene, meaning they have a spare if one is faulty. Men don’t have that back-up. The result is that more cells may begin to malfunction with time, putting men at greater risk of disease.

Among the other alternatives is the “jogging female heart” hypothesis – the idea that a woman’s heart rate increases during the second half of the menstrual cycle, offering the same benefits as moderate exercise. The result is delayed risk of cardiovascular disease later in life. Or it could also be a simple matter of size. Taller people have more cells in their bodies, meaning they are more likely to develop harmful mutations; bigger bodies also burn more energy, which could add to wear and tear within the tissues themselves. Since men tend to be taller than women, they should therefore face more long-term damage.

Testosterone might make our bodies stronger in the short-term, but the same changes also leave us open to heart disease, infections, and cancer later in life. “For example, testosterone might increase seminal fluid production but promote prostate cancer; or it might alter cardiovascular function in a way that improves performance early in life but leads to hypertension and atherosclerosis later,” says Gem.

Not only do women escape the risks of testosterone – they may also benefit from their own “elixir of youth” that helps heal some of the ravages of time. The female sex hormone oestrogen is an “antioxidant”, meaning that it mops up poisonous chemicals that cause cells stress. In animal experiments, females lacking oestrogen tend not to live so long as those who have not been operated on – the exact opposite of the male eunuch’s fate. “If you remove a rodents’ ovaries, then the cells don’t repair against molecular damage quite as well,” says Kirkwood.

Carnegie Mellon:
We propose that women's longevity edge over men may simply be a by-product of genetic forces that maximized the length of time during which women could bear and raise children and perhaps assist with grandchildren as well. Moreover, male longevity may simply be a function of the fact that men must carry the genes that ensure longevity to pass them on to their daughters. Thus, the necessity of female longevity in the human species may be the force that has determined the natural life span for both men and women.

THE VERDICT

Scientific American:
The biological advantage that women have is taken as a certainty, because the mortality of males is higher than that of females from the very outset of life: during the first year of life, in the absence of any outside influence which could differentiate mortality between the sexes, male mortality is 25 to 30 percent greater than is female mortality. The genetic advantage of females is evident. When a mutation of one of the genes of the X chromosome occurs, females have a second X to compensate, whereas all genes of the unique X chromosome of males express themselves, even if they are deleterious. More generally, the genetic difference between the sexes is associated with a better resistance to biological aging. Furthermore, female hormones and the role of women in reproduction have been linked to greater longevity. Estrogen, for example, facilitates the elimination of bad cholesterol and thus may offer some protection against heart disease; testosterone, on the other hand, has been linked to violence and risk taking. Finally, the female body has to make reserves to accommodate the needs of pregnancy and breast feeding; this ability has been associated with a greater ability to cope with overeating and eliminating excess food.

But the recent mortality trends have gone much farther than the mere recovery of an original advantage, creating instead a new advantage of greater magnitude for women. Observations indicate that the growing excess male mortality in industrial countries could be explained by the rise of so-called "man-made diseases," which are more typically male. These include exposure to the hazards of the workplace in an industrial context, alcoholism, smoking and road accidents, which have indeed increased considerably throughout the 20th century.

More information:
» Health Research Funding: "Why Married Men Live Longer Than Single Men"
» USA Today: "Life expectancy in the USA hits a record high"
» Steven N. Austad, Kathleen E. Fischer. "Sex Differences in Lifespan." Cell Metabolism. Volume 23, Issue 6, p1022–1033, 14 June 2016. DOI: http://dx.doi.org/10.1016/j.cmet.2016.05.019.

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