Most gerontologists agree that aging is not a disease. Yet a growing number of biologists reject this proposition, and serious work on slowing the process of aging is now under way in the laboratory. In other words, they treat aging as if it’s a curable pathological condition. Of course, no one has ever defined exactly what a “disease” is, so it’s hard to prove the point one way or another (Moody & Hayflick, 2003).
Caloric restriction in mice has similar effects even when it is begun in midlife. Rodents live longer if they eat a diet with 40% fewer calories than normal, as long as their diet remains otherwise nutritionally sound. When caloric intake is restricted, age-related deterioration slows down, and age-related diseases, such as kidney problems and autoimmune syndromes, are diminished (Bronson & Lipman, 1991). The rats’ condition does not deteriorate until late in a long life. Under such a diet, both average life expectancy and maximum life span increase by 30%. Apparently, the rate of acceleration of aging has been reduced.
What accounts for this dramatic, well-established impact of dietary restriction in enhancing longevity? The longevity gain is achieved not through reduction in any specific component of the diet, but simply because of fewer total calories consumed. One possible explanation is that caloric reduction slows metabolism, or the rate at which food is transformed into energy (Demetrius, 2004). With caloric reduction, the basic biological clock slows down. But we cannot be sure of this explanation because caloric restriction is consistent with many different mechanisms of biological aging, including DNA, free radicals, and a stronger immune system. The results are clear enough for rodents, and experiments with primates have begun to confirm that caloric restriction is effective there as well (Couzin, 1998). However, more recent research has found just the opposite: Caloric restriction with rhesus monkeys did not contribute to “improved survival” (Mattison et al., 2012).
In human terms, caloric reduction would mean surviving on a diet of 1,400 calories a day, but, in return, it would mean, in theory, gaining 30 extra years of life. To achieve this goal, Roy Walford (1986), one of the premier investigators of the biology of aging, has proposed a so-called high-low diet that incorporates high nutritional value with low calories.
A similar approach is suggested by cryobiology, or the study of organisms at low temperatures. Lowering internal body temperature can increase life span in fruit flies as well as vertebrates, such as the fence lizard, an animal that lives twice as long in New England as its cousins do in sunny, warm Florida. Experiments with fish demonstrate that with lower temperature, life span is prolonged in the second half of life. Lower temperature can significantly reduce DNA damage. We don’t yet know whether cryobiological processes apply to warm-blooded animals like humans. However, calorie restriction also seems to lower body temperature a small amount. Calorie-restricted mice have a lower average body temperature, and the temperature changes according to biorhythm.
Caloric restriction somehow protects genes from damage by the environment and perhaps strengthens the immune system. Caloric restriction also reduces the incidence of cancer. The experimental findings on caloric reduction converge with what is known about indirect regulation of genetic expression that controls the aging process.
Some recent evidence in human clinical trials suggests that caloric restriction, without malnutrition, can reduce vulnerability to disease and slow the process of aging in human beings. But the gains here come from dramatically changing a person’s diet. It is reminiscent of the old joke: “Doctor, if I follow your low-calorie diet, will I live longer or will it just seem longer?” Biologists are now looking for the cellular and molecular mechanism by which caloric restriction works, offering the possibility that lifespan extension could be achieved by interventions other than diet (Anderson, Le Couteur, & de Cabo, 2018).
Thinking Critically: Caloric Restriction
Would you be willing to experiment in your own life by restricting the number of calories you consume, not for weight loss purposes, but in the hopes of living longer? For what duration of time would you run your self-experiment? What changes in your lifestyle would you need to make in order to be successful (in addition to restricting your calories!)? What are some of the challenges you might face? Are there any other “lifespan extension” interventions you’d be willing to try?
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Genetic Approach
Many lines of evidence point toward the central role of genetics in fixing the longevity of each species, although for any individual, length of life is the result of both genetic and environmental factors. We often think of genetic inheritance as the element that is fixed and unalterable, but some genetic studies have shown a dramatic ability to improve maximum life span over generations.
For example, studies have been conducted on bread mold, fruit flies, mice, and nematode worms. In all these species, genetic manipulation has been shown to modify maximum life span. Some mutated forms of nematode worms have exhibited substantial increases. Among mice, large differences in average life expectancy and maximum life span exist among different strains because of hereditary differences. In the fruit fly, scientists have achieved an increase in average as well as maximum life span by using artificial selection as a breeding technique.
Some recent genetic experiments have produced astonishing gains in longevity. For example, Michael Rose, a population geneticist, used artificial selection to produce fruit flies with a life span of 50 days (double the normal average of 25 days); the equivalent would be a human being living to 240 years of age. Rose, in effect, has in the laboratory mimicked an increase in the evolutionary rate of change. As a result, successive generations of fruit flies passed along genes favoring prolonged youth and longevity (Rose, 2005).
Thomas Johnson, a behavioral geneticist, went further and altered a single gene (known as Clock-1) out of the roundworm’s 10,000 genes. He also achieved a doubling of the worm’s 3-week life span (Johnson, 1990). Still other studies suggest that in some fruit fly populations, the risk of mortality may decrease with advancing age, a finding that challenges previous assumptions about maximum life span (Barinaga, 1992). These dramatic successes, through breeding or direct genetic manipulation, point to the way that genetic change may have come about rapidly through natural selection.
Whether any of these findings can be applied to humans is, again, unknown, but we can draw some conclusions about the genetics of aging. For instance, in at least several of the animal studies cited here, the genes involved governed antioxidant enzymes and mechanisms for repair of damage to DNA, which have been at the center of several theories about the biology of aging. Second, in the species benefiting from genetic change, a small number of genes have been involved in determining longevity. Thus, these results could possibly be applied to higher animal species.
New horizons for genetic application are already visible. Scientists have found a way to double the life of skin cells by switching off the gene that regulates production of a specific protein responsible for manifestations of aging. A similar method of genetic engineering has been used with tomatoes, permitting them to be stored and shipped without decay. The key here is the so-called mortality genes, which determine the number of times that cells divide. Thus, this intervention addresses the Hayflick limit, which remains central to aging at the cellular level. Even without affecting maximum life span, this sort of gene therapy could have major applications in the future, perhaps leading to a cure for age-related diseases such as Parkinson’s, Alzheimer’s, and cancer.
The recent Human Genome Project has produced a comprehensive map of the entire sequence of genes on the human chromosome. Genetic engineering could draw on that knowledge in ways that might dramatically change what we have thought of as the process of aging and even our assumptions about the maximum human life span. Such speculations, however, belong to the future.
Global Perspective
Blue Zones for Longer Life
When we think of Italy, we often think of pizza or the ancient city of Rome. But if you’re thinking about longevity, think instead about the Italian island