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James Curtsinger

The oldest of the old "are the survivors," says U biologist James Curtsinder. "They're past the heart attack and cancer years, and they've avoided the main causes of death."

The science of longevity

U researcher learns from the oldest of the old

by Jennifer Amie

Jan. 12, 2007

Shrews live 18 months, Canada geese live 25 years or more, elephants commonly reach their 60s, and tortoises can outlast them all, with a life span of more than 150 years. But how long can humans live? This question took root in the mind of biologist James Curtsinger when he met the oldest man in the world.

Curtsinger, a professor in the University's Department of Ecology, Evolution and Behavior, was introduced to Christian Mortensen in California in 1997. Mortensen would die the following year at age 115 years and 252 days. "He enjoyed smoking and had an excellent sense of humor," recalls Curtsinger, who had arrived at Mortensen's nursing care facility bearing cigars. Born in Denmark in 1882, Mortensen could remember sailing into New York harbor in 1903, at the age of 21, and being processed at Ellis Island. Age had taken its toll on his short-term memory, however, and he suffered from cataracts and hearing loss. "Meeting him was an uplifting experience, but it was also sobering because he was no longer self-sufficient," says Curtsinger, who marveled at Mortensen's longevity. He began to wonder: What made Mortensen so special that he could live to such an advanced age?

Curtsinger, whose background is in population genetics, teamed up with demographic researcher James Vaupel to study the oldest of the old--the centenarians at the outer edge of the human life span. In particular, they set out to investigate a commonly held belief about life expectancy: that a person's risk of dying increases exponentially with increasing age. "What this implies," says Curtsinger, "is that there is an age at which the risk of death is so large that almost no one survives beyond it." But the oldest of the old, like Mortensen, defied those odds to such a degree that Curtsinger and Vaupel began to wonder whether this so-called "wall of death" existed at all.

The two researchers took the unusual step of pursuing both demographic research, conducted by Vaupel, and laboratory experiments conducted by Curtsinger. Together, they launched a 15-year project, funded by the National Institutes of Health, to compile data on mortality rates among humans and among experimental colonies of fruit flies.

"Meeting him was an uplifting experience, but it was also sobering because he was no longer self-sufficient," says Curtsinger, who marveled at Mortensen's longevity.

Finding reliable data on human life spans proved to be tricky. In the 1970 United States census, for example, 100,000 people reported that they were centenarians. "The real number," says Curtsinger, "was closer to 4,800." It turns out that the oldest people tend to over-state their age, perhaps rounding up for reasons of prestige. With that in mind, Vaupel turned to the most reliable data he could find for his demographic studies: written population records from Sweden dating back several hundred years.

For his part, Curtsinger began raising experimental colonies of fruit flies in the laboratory. "To get an accurate picture of mortality at the oldest ages," he says, "you need to start with an enormous population--50,000 to 100,000 flies for each experiment." Over time, after most of the flies died off, Curtsinger was able to record the mortality rates of the remaining, longest-lived flies.

Both the laboratory experiments and analysis of the Swedish population records revealed the same unexpected phenomenon: the risk of death increased exponentially with age at first, but at the oldest ages, the risk of death leveled off. There was no "wall of death." Instead, after a certain age, mortality rates hit a plateau.

Evolution and aging

While there are many factors that affect human senescence and longevity--including advances in health care, access to health care, and environmental and social conditions--genes, which are the cause of inherited human diseases, play a significant role in what happens to individuals as they age. In fact, evolutionary theory offers a convincing explanation for why late-onset diseases such as Alzheimer's occur in the population.

The Nobel Prize-winning immunologist Sir Peter Medawar first described the effects of natural selection on diseases of old age. Inherited diseases that affect a young person's ability to survive and reproduce will be strongly selected against, and weeded out of the population over time. Diseases that strike in old age, well past the reproductive years, are not strongly selected against. This allows harmful mutations with a late onset to accumulate and spread through the population over time.

What that means for humans, says Curtsinger, is that if you live to be 100, your risk of dying is 50 percent every year thereafter. At age 105 or 110, your risk is still 50 percent--it doesn't increase. This suggests that the oldest of the old are the most vigorous among us. "They are the survivors," Curtsinger says. "They're past the heart attack and cancer years, and they've avoided the main causes of death."

Further research with experimental systems using fruit flies, nematodes, and mice is helping to identify which genetic factors enable these survivors to live so long. In ongoing studies, Curtsinger is examining the genetics of fruit fly populations that have been selected for long life. These flies live twice as long as their normal counterparts and, essentially, Curtsinger is asking the same question about them that he once asked about Christian Mortensen: What makes them so special? So far, he has discovered that at older ages, antioxidant genes and genes related to immunity are more active in the longest-lived flies.

Whatever the secret to his longevity, is turns out that Mortensen was at the leading edge of a trend that affects us all. Overall human life expectancy has increased dramatically over the past 160 years. According to Vaupel, in 1840, Swedish women held the record for longevity with a life expectancy of 45 years; by 2000 Japanese women enjoyed a life expectancy of 85 years. In the United States, life expectancy is expected to rise past 85 by the year 2060, up from 77 today, says Curtsinger. Worldwide, the rate of increase in human life span shows no sign of slowing.

These data, along with the discovery that there is no "wall of death"--or set age beyond which almost no one can survive--suggest that there is no well-defined upper limit to the human life span. How long can humans live? The likely answer, says Curtsinger, is longer and longer as time goes by.