Contact: John Easton
Fundamental (But Forgotten) "Law of Mortality" Resuscitated
HUMANS, BEAGLES AND MICE - and probably most other sexually reproducing species - tend to die on identical schedules but on different time scales. The probability of dying is high at birth, declines until puberty and then increases at an exponential rate (for humans, doubling every seven years) until very old age when the rate of increase slows.
This characteristic pattern of human mortality was first described by British actuary Benjamin Gompertz in 1825. His attempts to verify this "law of mortality" and to extend it to other species became a major scientific focus for more than a century until it was abandoned in 1935 because no one could muster the data to prove it.
Now, researchers from Argonne National Laboratory and the University of Chicago Medical Center have assembled powerful new evidence, gathered from some unusual databases, which supports Gompertz's theory.
Their research - a 12,000-word, 34-page highly controversial paper - is published in the June issue of Population and Development Review.
Gompertz and his successors failed because they were unable to separate the biological effects of aging, what Gompertz called "a deterioration, or an increased inability to withstand destruction," from environmental causes of death such as mishaps, poverty and pathogens.
"The mortality patterns these early demographers were trying to describe did not exist for large populations of humans or animals before the middle of the twentieth century," said Bruce Carnes, Ph.D., from the Center for Mechanistic Biology and Biotechnology at Argonne National Laboratory.
But in the second half of this century, the convergence of peace and prosperity with public health measures such as improved sanitation, widespread immunization and antibiotics has for the first time in history allowed the vast majority of humans to grow old, to deteriorate - in essence, to wear out.
At the same time, protective environments created for household pets, zoo and laboratory animals have created similar conditions for small populations of other species, sheltering them from environmental causes of death.
Records at Argonne Laboratory for large groups of sheltered animals allowed the research team finally to revive Gompertz's search for a law of mortality. The researchers turned to extraordinarily detailed, long-term, multi-generational records for 13 strains of laboratory mice, with widely varied lifespans, and a large colony of beagles that were used at Argonne from 1953 to 1993 as control groups (unexposed animals) for studies on the biological effects of radiation. For human mortality, the researchers used an Argonne database from a carefully compiled epidemiological study of women exposed to radiation while working in the radium industry.
When they compared the mortality patterns for each species - focusing only on animals that died from aging-related causes and not on those killed by something in their environment - and adjusted for differences in lifespan, the resulting mortality curves were statistically indistinguishable.
"They fit the Gompertz model, and each other, like a glove," said Jay Olshansky, Ph.D, research associate in the department of medicine at the University of Chicago. "Clearly, Gompertz was on the right track," he added. "There is a consistent pattern of death for animals that survive past sexual maturity. But this pattern becomes visible only under the rare condition of extended survival for a large number of animals protected from external causes of death."
The pattern makes perfect sense from an evolutionary standpoint, say the researchers. In hostile environments, which have probably been the rule throughout history, natural selection favors early reproduction. That strategy is locked into the genome of each species. Living beyond the period of producing and nurturing offspring offers the species no survival advantage. Thus, while animals are hardly designed to fail after the reproductive period, neither are they built to last indefinitely.
The researchers like to compare this mortality pattern to that of an "Indy- style" race car, designed to operate at peak efficiency for 500 miles, being driven long after the race.
Damage begins as soon as the engine starts, "so these cars are over-engineered to make certain the weakest links will complete the critical distance," suggested Carnes. "Failures after the race, the automotive equivalent of reproduction, don't matter enough to merit the extra weight and added expense of building a more durable car.
"So one would expect to see different systems begin to break down shortly after 500 miles," added Carnes. "Mechanical breakdowns would become steadily more common as wear accumulated, peaking at, let's say, 1,500 miles. A few of the more well-engineered or more carefully driven autos might limp on for a while after that."
The human equivalent of the 1,500-mile marker is about age 85, similar to earlier projections of the maximum average lifespan suggested by Carnes and Olshansky in a paper in Science in 1990 (2 Nov.).
"If a law of mortality does in fact exist," suggested Olshansky, "we may be soon approaching the limit in our ability to extend the average human lifespan."
While not exactly good news, the results of this study do suggest that budget projections for age-related programs such as Social Security or Medicare that are based on a continuing increase in the average life span may be off target. Even if we continue to reduce the environmental causes of death and find new ways for modern medicine to delay the onset of age-related diseases, "we are simply not designed to run forever," say the authors.
"It's easy for an individual to speed up his own senescence by smoking, avoiding exercise, eating the wrong foods, alcohol excess," added Carnes. "But it's hard for an entire society to slow it down. There are a lot of crucial systems in each of us that can fail and once one of them does it doesn't matter if all the others are running perfectly."
The researchers conclude that gains in extending life are of little value if they are not accompanied by comparable gains in the quality of life.
Funding for this research was provided by the Department of Energy, the Social Security Administration and the National Institute on Aging.