Sci. Aging Knowl. Environ., 18 September 2002
The Shrimps Shall Inherit the Earth
Smaller youths live longer
Runts of the world have long suffered the taunts and physical domination of their taller, hulkier brethren. Well, the puny and the petite might have the last chortle yet. A new report confirms that peewees outlast titans--among rodents, at least--and offers the first hint that body weight at an early age correlates with an animal's life expectancy.
The results add to the growing body of evidence that size is linked to longevity, says physiologist Andrzej Bartke of Southern Illinois University in Carbondale. One of the investigation's strengths is its longitudinal design: Whereas most studies assess size at one time point or life stage, the new one tracks the rodents' weight month by month from birth to death. As a result, the investigators discovered that "body weight at a relatively early age is what most clearly and most strongly associates with longevity," Bartke says--the work's most novel finding.
To ensure that the results would not apply to only a single genetic type, Richard Miller, a gerontologist at the University of Michigan Geriatrics Center in Ann Arbor, and his colleagues studied 598 mice that were the grandchildren of mixed matings among four common strains of laboratory animals; thus, like human individuals, each rodent in the study was genetically unique, making it less likely that the results would apply to only a single genetic type.
A low body weight at as early as 2 months of age, the equivalent of adolescence in humans, went hand in hand with greater longevity, the team reported in the 16 September issue of Aging Cell. "It's the earliest predictor [of longevity] we know about," says toxicologist Angelo Turturro of the National Center for Toxicological Research in Jefferson, Arkansas. The animals' median survival time--the time frame in which half of the rodents had died--stretched by 36 days for the light mice compared to the heavy ones, meaning that the pipsqueaks reaped a 4.3% bonus in median life expectancy. In an additional study, Miller and colleagues calculated that every extra gram that one of his mice puts on early steals 6 days of its life.
Body weight is determined by an animal's stature--its height or, in this case, length--plus other components, including how much fat the creature carries. The current work does not address which of these factors correlates with life-span, but Miller has some ideas. Although the scientists didn't measure how long or how fat the mice were, they suspect that flab, which conceivably could reduce longevity through its many connections to life-threatening diseases such as diabetes, is not the key factor. The mice reach full stature by 2 to 4 months of age, Miller says, but they keep putting on fat as they mature, achieving maximum body weight on average by 14 months old. Yet, the link between size and longevity was strongest in the first 12 months and not at the later ages when obesity would be most notable. These results have led Miller to speculate that stature is more important than fat.
The amount of time that these little mice gained wasn't as impressive as the life-extending benefits in rodents that carry dwarf genes or in animals that are unusually small because they eat less. The Ames dwarf, for instance, survives on average 50% longer than a normal mouse; calorie-restricted mice typically last 40% longer than compatriots that eat all they want. Still, the survival difference associated with diminutive size isn't trivial: It's greater than the gain in life expectancy that would result from preventing cancer in humans, Miller points out. If cancer never occurred after age 50, the average white American woman would live three more years--lengthening her total life-span by nearly 4%.
Although larger species tend to live longer than smaller ones, the idea that punier is better for longevity within a species is far from new. Ask any dog breeder. "The breeds that are small in body size--the miniature poodles and schnauzers, the Chihuahuas and the like--are substantially longer lived than the bigger dogs, like the wolfhounds and the Newfoundlands," says Miller. The same appears to be true in horses, he adds. In people, the connection between height and life-span is confusing and controversial. One survey of statistics on deceased baseball players found that taller athletes died younger. Other reports suggest that towering individuals tend to outlast their undersized peers. However, when results are adjusted for socioeconomic factors that influence nutrition, growth, and access to health care, the apparent superior longevity of the tall disappears or even reverses, says Miller. For example, some research indicates that shorter people are less likely to die of cancer.
A clearer picture has been emerging in work with rodents. In 1990, Ghanta Rao, a toxicologist at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, and colleagues reported that over an 11-year-period, Fischer 344 rats used in toxicology testing had been growing faster and bigger--and dropping dead earlier and earlier; experts later realized that the lab strain had inadvertently been bred for increasingly large size over the decades. Earlier this year, Canadian biologist C. David Rollo of McMaster University in Hamilton, Ontario, plotted data on 796 cohorts of mice and rats from a fairly comprehensive selection of 20th century studies and uncovered a strong linear relation: The bigger the animal's maximum weight, the sooner it expired. In other work, Rollo found that giant transgenic rats, engineered to crank out growth hormone, age rapidly and die young.
Other work establishes that size at different ages correlates not only with longevity but also with diseases of old age. In studies on mice, Turturro and colleagues discovered that "animals that were heavy at 12 months of age would die of liver tumors," Turturro says. "But if they were heavy at 2 months of age, they would die of leukemias or lymphomas."
Miller's results support the hypothesis that the process of growing old is shaped by changes that occur in an animal's salad days. If confirmed by other studies, says Miller, the new data would mean that "a good chunk" of the differences that govern the rate of aging and vulnerability to disease in mice--and possibly humans--is influenced by factors in play during adolescence or early adulthood.
Such a scenario raises the tantalizing prospect of manipulating these as-yet-unknown factors at a relatively young age to prevent disease decades hence. "If we could show that something, some hormonal changes or cellular growth patterns, in little kids makes a huge difference in whether they're likely to die at 70 or 80 or 90, that would be of real interest," Miller says. In principle, researchers might discover a way to uncouple such longevity-enhancing factors from size, allowing people to extend their life-spans while retaining the ability to play basketball.
Probing for possible mechanisms that explain how size affects longevity, Miller and colleagues found that the small adolescent females--but not the small males--bore a physiological similarity to calorie-restricted and dwarf mice: low blood concentrations of the growth hormone IGF-1. The investigators also scanned the animals' DNA in a first step toward targeting the genes that might be at work. By comparing particular DNA sequences in the mice, the researchers identified four genetic regions that appear to be associated with body size.
Genes that rein in an animal's early growth rate, Miller speculates, might delay aging by spurring changes that protect cells from stress and disease. Research has demonstrated that mutations conferring extra longevity in the roundworm, C. elegans, also make it more resistant to potentially lethal conditions, such as exposure to ultraviolet radiation. Long-lived yeast, fruit flies, and calorie-restricted rats also show unusual hardiness when exposed to reactive oxygen species (see "The Two Faces of Oxygen", Longo Perspective, Johnson Review, and Genes/Interventions Database entries on SCH9, MTH, and daf-2).
Whatever the correct explanation for the size-longevity relation, Miller says he hopes that his findings will encourage experts on aging to pay more attention to growth and maturation during young adulthood. And if diminutive stature does someday prove to assure an extended lease on life, maybe 90-pound weaklings will finally get some respect. Contrary to that old Randy Newman song, short people would not only have every reason to live, but they'd have more time to do it.
September 18, 2002
Ingfei Chen is a 5'2" science writer in Santa Cruz, California. Her proverb-quoting 5'41/2" father has always said that the bigger they are, the harder they fall.
Suggested ReadingBack to Top
Citation: I. Chen, The Shrimps Shall Inherit the Earth. Science's SAGE KE (18 September 2002), http://sageke.sciencemag.org/cgi/content/full/sageke;2002/37/nf10
Science of Aging Knowledge Environment. ISSN 1539-6150