Term Paper #2
The Effects of Calorie Restriction on Aging
by Jessica Swantek
For ages, humans have been searching for ways to counteract the aging process. The legendary fountain of youth generated much attention in the past, and more recently, thousands of dollars have been spent each year on creams, pills, plastic surgery, and various forms of therapy designed to make one look and feel younger. So far nothing has been proven to reverse or even retard human aging, but scientists are finally catching a glimpse as to a dietary manipulation technique that might work.
In the 1930s, Clive McCay, a scientist at the laboratories at Cornell University, experimented on his rats by feeding them less than they would ordinarily take for themselves, but without depriving them of nutrition to the point of starvation. He found that the food-deprived rats lived considerably longer than expected for a standard rat's life span, and about 33 percent longer than his control group of rats, which were fed as much as they wanted to eat (Weindruch 46). McCay didn't fully understand his results, and although published, they were generally disregarded by the science world (Man Immortal).
Years later, Roy Walford, a nutritionist working at the University of California at Los Angeles Medical Center, came across the documentation of McCay's experiments, and, using modern technology and mice instead of rats, picked up where McCay had left off (Man Immortal).
Walford found that for the best results to achieve the longest life extension in his mice with the fewest negative side effects, calories should be restricted by 30 percent of what would be taken freely by the mice, and essential nutrients must still be consumed (Mlot 162). Dietary reduction of other things, such as fat intake, may be beneficial to health, but it does nothing to extend life span (Whitlock). Mice usually live anywhere from 38 to 40 months. When calories were restricted by 30 percent, they lived from 56 to 57 months, which is roughly equivalent to 147 years old in human terms (Man Immortal).
Among his findings, Walford discovered that the mice lived about 30 percent longer than average, weighed about 30 percent less than usual, had lower blood pressure, lower levels of serum cholesterol, lower concentrations of circulating glucose, lower triglyceride concentrations, lower insulin levels, and greater insulin sensitivity. In short, their bodies were becoming extremely efficient at utilizing the few calories that were put into it (Weindruch 49). The animals had stronger immune systems, and the onset of common late-life diseases, such as certain cancers, were held off as well (Weindruch 48).
Why It Works
Walford knew that reducing calories was slowing metabolism in the mice and improving their health in general, but he was unaware of exactly what was causing the slowing of the metabolism, and why it caused the extension of life span in the mice. In order to explain what was triggering the results, we first look at worms.
Nematodes have an average life span of 14 days. However, at times when food is scarce, such as when overpopulation occurs, the seemingly simple worms have the ability to switch into a state of suspended animation known as the Dauer phase, “dauer” being the German word for “durable,” during which they can live for two months or more, which is over four times longer than usual. Scientists such as Cynthia Kenyon at the University of California at San Francisco are studying the nematodes and their connection with humans (Roush 897).
Kenyon and her colleagues have found that there is a gene responsible for the worms changing into their Dauer phase. It is called DAF-2, for Dauer-formation defect 2. The gene senses when there is not enough glucose present, and then acts as a switch to begin the Dauer phase. More recently it has been found that the DAF-2 gene shares 35 percent of its amino acid sequence with the human insulin receptor, making it the worm equivalent of our insulin receptor (Roush 897). So when there is insufficient glucose in the human body, there is less insulin secreted in response, and the human insulin receptor detects that there is not enough insulin, and acts as a switch to slow our metabolism and cellular respiration.
Metabolism is defined as the energy-releasing breakdown of molecules. Energy is created through cellular respiration. Cellular respiration takes place in the mitochondria of the cell, and uses oxygen to make energy in the form of ATP. During ATP synthesis, an electron is removed from an oxygen molecule during the electron transport chain, leaving an unpaired electron. These molecules with one unpaired electron are known as free radicals (Kotulak and Gomer).
Free radicals are very unstable molecules. The byproduct of burning oxygen in cells, they severely damage essential enzymes, molecules, organelles, and DNA (Weindruch 49). The molecule wants to have a complete pair of electrons, so it steals an electron from another molecule so that it becomes stable. However, then the second molecule has an incomplete set of electrons, and must rip an electron off of a third molecule, thus causing a very destructive chain reaction that eventually ends when two free radicals come together, but wreaks cellular havoc in the meantime (Kotulak and Gomer).
Our bodies produce antioxidants which combat free radicals and repair free radical damage, and antioxidants are also present in certain foods, especially vitamins C, E, and A (Dietary Manipulation). However, after a point the antioxidants simply cannot keep up with the amount of free radical damage inflicted. When cells become irreparably fractured by free radicals, they die, which results in human aging (Man Immortal). Free-radical damage is also responsible for diseases such as cataracts, heart disease, and some cancers (Kotulak and Gomer).
Caloric restriction counteracts these age-causing processes. So, if fewer calories are ingested, which causes a gene to tell the metabolism and respiration to slow down, fewer free radicals will be produced in the mitochondria, so cells will undergo less oxidative damage, and life will be extended, which is how caloric restriction treatment works.
Calorie restriction experiments have now been performed on organisms ranging from water fleas to guppies to monkeys (Weindruch 46). One ongoing experiment that seems significant is currently being done on rhesus monkeys at the University of Wisconsin at Madison with funding from the National Institute on Aging. Since the monkeys ordinarily live to be around 40 years old, it will be some time before end results are seen, but scientists already observe the effects of calorie restriction in blood pressure, cholesterol, and basic observed markers of aging in the 17-year-old monkeys (Mlot 162). This experiment is considered to be particularly important because of the primates' close relation to humans. Scientists will be able to more accurately predict what results of calorie restriction on humans could be by observing the rhesus monkeys over the next few decades. A similar experiment using squirrel monkeys has also been underway since 1987 in Baltimore, Maryland (Dietary Manipulation).
Application in Humans
When Roy Walford finished his preliminary experiments on mice, he knew that he had stumbled across some very important information, and wondered if a parallel extension of life could be observed in humans under similar conditions. As it turned out, he was able to conduct his experiments on humans sooner than he had expected. Walford was one of eight human subjects sealed inside Biosphere 2 in September of 1991. The team produced far less agriculturally than had been anticipated and were therefore forced to cut back on their food intake. Walford, being a nutritionist, put himself and the seven other Biospherians on a diet that closely reflected the 30 percent calorie reduction that he used on his mice, also making sure that essential nutrients were not cut out of the diet. As expected, Walford recorded parallel results in the humans (Walford).
Walford has since published several books on caloric restriction as a means for human life extension, such as The 120 Year Diet: How to Double Your Vital Years, and has even designed a computer program for the purpose of constructing what he considers an appropriate diet for this purpose (Dietary Manipulation). He has also experimented on himself: He has been on a calorie-restricted diet for the past ten years, and at age 72, believes that he has added five or six years to his life already (Man Immortal). Most scientists, however, agree that it is too soon to accurately conclude that caloric restriction would be safe and successful for humans.
Even if caloric restriction is approved as a feasible means for life extension in the future, there will probably not be many people willing to use it. Reducing one's calorie intake by 30 percent is a big dietary change, and ensuring that essential nutrients are still ingested requires careful planning. It is not necessarily easy to get used to. Subjects do feel hunger, and because of the reduced calorie intake, they have less energy and are not able to have extremely active lifestyles (Man Immortal). It's hard to imagine many people adopting such a drastic diet change, when even seemingly simple health improving measures, for example consuming five servings of fruit and vegetables a day, have had few takers (Mlot 163). And risks must be taken into consideration, such as the inability to reproduce when one's body processes are focused solely on survival (Weindruch 52).
What the Future May Hold
Although surprising to some, what may come to the forefront of life extension research is Cynthia Kenyon and her UCSF nematodes. The scientists there have been tinkering with the DAF-2 gene and have been able to get the worms to go into the Dauer phase without being first deprived of food. This indicates that perhaps in the future, we will be able to manipulate the human insulin receptor to slow respiration to the point of significant life extension without changing our diet very much (Man Immortal).
There will undoubtedly be more caloric-restriction experiments on human subjects in the future, but no matter what the means, with scientists learning more every day about how basic life processes work and how to change them, plus the tremendous advances in medicine both recently and soon to come, the future of the human race might live to see more birthdays than its ancestors ever dreamed of.
Delaney, Brian Manning.”Calorie Restriction FAQ.” Calorie Restriction for the Purpose of Retarding Aging. 30 March 1998. <www.infinitefaculty.org/sci/cr/cr/htm> (23 May 1998).
“Dietary Manipulation of Aging.” Life Extension Magazine June 1995. <www.lef.org/shop/95jun1.htm> (23 May 1998).
Kotulak, Ronald and Peter Gomer. “Scientists Try to Tame Molecular Sharks.” Chicago Tribune 11 December 1991. <tular.nist.gov/week0/ch0731/news/aging/ aging6.htm> (20 May 1998).
“Man Immortal.” Dir. Howard Reay. Prod. Joanne Reay. TLC. New York. 1997.
Mlot, Christine. “Running on One-Third Empty.” Science News 15 March 1997: 162-163.
Roush, Wade. “Worm Longevity Gene Cloned.” Science 15 August 1997: 897-898.
“Slowing the Process of Aging.” Fact Sheet: Normal Changes of Aging. <www.biorap.org/ rg/rgageslowp.html> (23 May 1998).
Walford, R. L. “Abstract: Biosphere 2.” 1992. <www.walford.com/abstrct2.htm> (23 May 1998).
Weindruch, Richard. “Caloric Restriction and Aging.” Scientific American January 1996: 46-52.
Whitlock, Kelli. “Researchers Find a Low-Fat Diet Does Not Prevent Age-Related Memory Loss.” 15 November 1996. <www.cats.ohiou.edu/~univnews/ months/nov96/125.html> (23 May 1998).
Excerpted from The Complete Idiot's Guide to Writing Well © 2000 by Laurie Rozakis, Ph.D.. All rights reserved including the right of reproduction in whole or in part in any form. Used by arrangement with Alpha Books, a member of Penguin Group (USA) Inc.