February 21, 2002 8:20 CDT
Cosmiverse Staff Writer
A combination of dietary supplements has been found to dramatically improve the activity, energy level, and cognitive function of elderly rats. The finding was made by researchers in the Linus Pauling Institute at Oregon State University and the University of California at Berkeley.
Details of the study, which was funded by grants from the National Institutes of Aging, were revealed Wednesday in three articles in the Proceedings of the National Academy of Sciences. Clinical trials with humans are ongoing to determine whether the compounds offer the same benefits to people.
The researchers used a combination of two compounds that occur naturally, acetyl-l-carnitine and an antioxidant, alpha-lipoic acid. Past research has shown that either of these compounds may be able to address some of the physical and mental deterioration associated with aging, but this research showed that a combination of the two works much better than either one separately.
"After just a month, older rats whose diet was supplemented with these two compounds were about twice as active as our control rats, which remained largely inactive," said Tory Hagen, an assistant professor in OSU's Linus Pauling Institute. "They also had a much better memory and cognitive performance, measured by their ability to remember objects and spatial orientation."
They discovered that old rats that were given the dietary regimen had an activity level similar to those of middle-aged rats. The scientists said that the findings build on years of research into the aging process and these compounds. One particularly vulnerable area of cellular change that is associated with aging seems to be the mitochondria where the cell's energy is generated. The OSU and Cal-Berkeley scientists think the mitochondria is sort of an "Achilles heel" for absorbing age-related damage, and that there could be ways to influence that process, Hagen said.
"It appears that some compounds, including carnitine and lipoic acid, can mask the metabolic problems caused by cellular aging and the natural oxidative process," Hagen said. "We're very excited about the research. This may have relevance to improving people's quality of life and health."
The major diseases that people die from, such as heart disease and cancer, are closely related to aging, as are diseases that can severely impact the quality of life, such as Alzheimer's disease and Parkinson's disease. Hagen said that like many complex metabolic processes, there cannot be a single, simple answer to the aging process. Some believe that the process is hormonal, in which cells no longer "communicate" with each other properly, and others credit it to genetics, in which cells become "senescent" after a finite number of programmed divisions.
However, the researchers at OSU and Cal-Berkeley are studying the idea is that aging is at least partly due to the natural process of oxidation in the body and "free radicals," that cause cellular damage.
"Oxygen is a double-edged sword," Hagen said. "We need it to live and it's essential to cell function. But oxygen can be converted into what we call reactive radical oxygen species, or free radicals. And they have the potential to mutate DNA and damage lipids and proteins."
The free radicals produced by metabolism are the same that result from nuclear radiation -- just as if humans were being irradiated throughout their lives. The process is such a natural part of life that cellular repair mechanisms have evolved to help fix or prevent the damage -- not the least of which are well-known "antioxidants" such as vitamin C.
"These cellular repair processes are not perfect," Hagen said. "Oxidative damage does occur, and we think there's strong evidence that this contributes to aging and some of the other problems associated with it, such as cancer, arteriosclerosis or neurodegeneration." A particular weak spot in the body may be the mitochondria in cells - a quasi-independent structure similar to bacteria with its own DNA.
"Mitochondria are the power plants of our cells, where raw fuels are converted into usable forms of energy," Hagen said. "Up to 90 percent of the oxygen we breathe is used by the mitochondria, as they perform many of the roles critical to cell function, such as producing energy, regulating calcium and even controlling cell life and death."
But Hagen says that mitochondria are also the main source of free radicals, and because they are right nearby the dangerous free radicals they just created, they're also often the first to be harmed. "This can be a vicious downward cycle, in which mitochondria create free radicals and then fall victim to them," Hagen said. "This loss of mitochondrial function and its impact on metabolic function is at least one part of what we call aging."
Hagen and his colleagues have found when studying rats that there is a major decline of mitochondrial function, a slower metabolic rate and reduced cognitive function. He has shown that the antioxidants that help protect mitochondria, specifically glutathione -- an intracellular antioxidant -- decline severely with age. His studies have shown that the cells of old rats are much more susceptible to age-related oxidative stress than those of young animals.
However, the newest studies are promising. Carnitine is an amino acid involved in fatty acid transport into mitochondria. Carnitine is a natural compound produced in the cell and obtained in the diet through meats and vegetables.
Research has already shown that rats fed this compound had improved mitochondrial function and overall activity level. In studies done in humans, carnitine has been demonstrated to improve balance and short-term memory, Hagen said. And another strong antioxidant, lipoic acid, found in green, leafy vegetables, appears to improve mitochondrial function.
The new study shows that a combination of these two compounds provides all these benefits at even higher levels than either one alone. "As people age and their mitochondrial function declines, they are even less able to resist the usual metabolic insults of life, just like rats," Hagen said. "But we're seeing that an intake of these nutrients in combination seems to restore the ability of cells and mitochondria to deal with environmental stresses, just about as well as they did when they were young."
"If we can better understand the process of aging and how to influence it," Hagen said, "we may be able to give people a way to maintain human health for as long as possible."
Source: Oregon State University;
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