FEATURE ARTICLE
Aging: A Biological Perspective
A variety of techniques extend the lives of model organisms, and similar approaches might help human beings stay healthy longer
Robert Arking
A Healthier Span
The lives of animals can be lengthened in three ways: increasing their early survival rate, increasing their late survival rate or delaying senescence. The first two approaches decrease the mortality rate at the beginning or end of life, respectively, but do not affect the basic aging process. Even with increased early or late survival, organisms age normally but seem to be somewhat more resistant to stresses that kill off their normal comrades. Humans who exercise, for example, survive at higher rates in early and middle life and experience a lower level of morbidity, or occurrence of disease, but they age normally, with no decrease in late-life mortality. Centenarians, on the other hand, live longer than most people, although no one would mistake a centenarian for a middle-aged person. Instead, centenarians age normally, but tend to be healthier than their ordinary fellows. Although athletes and centenarians provide interesting examples of increasing early and late survival rates, they shed little light on basic aging processes.
The most interesting alteration involves the third approach, delaying the onset of senescence. Many examples of this pattern exist in laboratory animals, but none in humans as yet. My colleagues and I, for instance, created long-lived strains of fruit flies through artificial selection—simply allowing only the longer-lived flies to breed with one another over several generations. When we compared ordinary and long-lived fruit flies, the average life was about 40 and 70 days, respectively. Likewise, the maximum lifespan increased from about 61 to 91 days. But how much of that added time is lived in good health? Let's call that good-health period the health span and make it the time from birth until ten percent of the initial population dies. For ordinary flies, the health span lasted 30 days, and it grew to 60 days in the long-lived flies. So the flies' health span doubled. Nonetheless, the senescent period—from the end of the health span until all of the flies died—remained the same, about 30 days, which is a smaller proportion of the maximum life span for the long-lived flies.
My lab's data on fruit flies demonstrate that the health span and the senescent span are separate phases of the life span. Moreover, these data reveal that increasing the health span can extend longevity. In fact, experiments from a wide variety of investigators show that delaying senescence can increase longevity in all of aging research's model organisms: common brewer's yeast (Saccharomyces cerevisae), nematode worms (Caenorhabditis elegans), fruit flies (Drosophila melanogaster) and laboratory mice (Mus musculus). For example, Martin Holzenberger and his colleagues at the Institut National de la Santé et de la Recherche Médicale in Paris inactivated the insulin-like growth factor type 1 receptor (IGF-1R) in mice, and the health span of females, (but not males,) increased by about 75 percent. Such findings suggest a built-in potential for increasing the health span, and this potential has been exploited experimentally as described below.
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