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Drugs are being tested to mimic caloric restriction's effects on longevity

A proven approach to slow the aging process is dietary restriction, but new research, "Rapamycin and Dietary Restriction Induce Metabolically Distinctive Changes in Mouse Liver, " published online March 18, 2014 in the Journals of Gerontology: Biological Sciences, helps explain the action of an antibiotic drug that appears to mimic that process -- rapamycin. The advance moves science closer to a compound that might slow aging and reduce age-related disease. Why take an antibiotic and make yourself more susceptible to becoming resistant to antibiotics instead of simply eating smaller portions and not wolfing down so many calories at each meal?

Which is better for longevity: Caloric restriction or drugs that mimic smaller food portions?
Photo by Sergi Alexander

Years after scientists have been trying to prove caloric restriction along with dense nutrition may be able to lengthen the lifespan, now scientists are coming up with a drug, a type of antiobiotic, that mimics caloric restriction so you don't have to eat less. But why spend money on a drug if you can save money by caloric restriction instead of your portion size as long as you had balanced nutrition?

A proven approach to slow the aging process is dietary restriction, but new research in the Linus Pauling Institute at Oregon State University helps explain the action of a drug that appears to mimic that process – rapamycin

Rapamycin, an antibiotic and immunosuppressant approved for use about 15 years ago, has drawn extensive interest for its apparent ability – at least in laboratory animal tests – to emulate the ability of dietary restriction in helping animals to live both longer and healthier. However, this medication has some drawbacks, including an increase in insulin resistance that could set the stage for diabetes. The new findings, published in the Journals of Gerontology: Biological Sciences, help to explain why that happens, and what could be done to address it.

They suggest that a combination of rapamycin and another drug to offset that increase in insulin resistance might provide the benefits of this medication without the unwanted side effect. Notice how big pharma suggests a drug on top of another drug instead of a nutrition-based solution? But how could food be used as medicine if there's less money in caloric restriction of something so simple as food as in vegetables and fruits as starters?

“This could be an important advance if it helps us find a way to gain the apparent benefits of rapamycin without increasing insulin resistance,” said Viviana Perez, according to the May 20, 2014 news release, "Research explains action of drug that may slow aging and related disease." Perez is an assistant professor in the Department of Biochemistry and Biophysics in the Oregon State University (OSU) College of Science.

“It could provide a way not only to increase lifespan but to address some age-related diseases and improve general health,” Perez said, according to the news release. “We might find a way for people not only to live longer, but to live better and with a higher quality of life.” Age-related diseases include many of the degenerative diseases that affect billions of people around the world and are among the leading causes of death: cardiovascular disease, diabetes, Alzheimer’s disease and cancer.

Laboratory mice that have received rapamycin have reduced the age-dependent decline in spontaneous activity, demonstrated more fitness, improved cognition and cardiovascular health, had less cancer and lived substantially longer than mice fed a normal diet

Rapamycin, first discovered from the soils of Easter Island, or Rapa Nui in the South Pacific Ocean, is primarily used as an immunosuppressant to prevent rejection of organs and tissues. In recent years it was also observed that it can function as a metabolic “signaler” that inhibits a biological pathway found in almost all higher life forms – the ability to sense when food has been eaten, energy is available and it’s okay for cell proliferation, protein synthesis and growth to proceed.

Called mTOR in mammals, for the term “mammalian target of rapamycin,” this pathway has a critical evolutionary value – it helps an organism avoid too much cellular expansion and growth when energy supplies are insufficient. That helps explain why some form of the pathway has been conserved across such a multitude of species, from yeast to fish to humans.

“Dietary restriction is one of the few interventions that inhibits this mTOR pathway,” Perez said, according to the news release “And a restricted diet in laboratory animals has been shown to increase their lifespan about 25-30 percent. Human groups who eat fewer calories, such as some Asian cultures, also live longer.”

A restricted diet in animals has been shown to increase their lifespan

Aside from a food intake in laboratory mice that’s about 40 percent fewer calories than normal, however, it’s been found that another way to activate this pathway is with rapamycin, which appears to have a significant impact even when used late in life. Some human clinical trials are already underway exploring this potential.

A big drawback to long-term use of rapamycin, however, is the increase in insulin resistance, observed in both humans and laboratory animals. The new research identified why that is happening. It found that both dietary restriction and rapamycin inhibited lipid synthesis, but only dietary restriction increased the oxidation of those lipids in order to produce energy.

Increase in insulin resistance with long-term use of rapamycin

Rapamycin, by contrast, allowed a buildup of fatty acids and eventually an increase in insulin resistance, which in humans can lead to diabetes. However, the drug metformin can address that concern, and is already given to some diabetic patients to increase lipid oxidation. In lab tests, the combined use of rapamycin and metformin prevented the unwanted side effect.

Can you believe instead of restricting calories and providing balanced nutrition, now there's a need for an antibiotic drug with side effects that can lead to diabetes, so another drug given to diabetics, metformin, is added on top of the first drug to "address that concern." Why not simply eat less food in the first place? The human body doesn't suffer from the lack of these drugs in nature. Scientists are researching to find out whether taking drugs such as metformin and rapamycin can treat aging and age-related diseases. The real goal needs to be alternatives, finding out what foods in the first place and how many calories of what edibles from nature can treat age-associated diseases without having the expense of two drugs instead of reduction in calories.

“If proven true, then combined use of metformin and rapamycin for treating aging and age-associated diseases in humans may be possible,” the researchers wrote in their conclusion.

At the present time more research is needed to see whether the theory and all that research in the laboratory is even true when it comes to humans. The National Institutes of Health supported the new research. Collaborators included researchers from Oklahoma University Health Science Center, the Oklahoma City VA Medical Center, University of Michigan-Flint, and South Texas Veterans Health Care System.

“There’s still substantial work to do, and it may not be realistic to expect with humans what we have been able to accomplish with laboratory animals,” Perez said, according to the news release. “People don’t live in a cage and eat only the exact diet they are given. Nonetheless, the potential of this work is exciting.” You also may wish to check out the Journals of Gerontology, Series A: Biological Sciences and Medical Sciences. Wouldn't it be cheaper and easier just to eat healthier and eat smaller portions of food?

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