‘Gene Chip’ Helps Unlock Aging’s Secrets
The everlasting hope of slowing the aging process is likely to get a lift from a study released today involving perpetually hungry lab mice and a futuristic “gene chip,” which together appear to shed new light on the only known method of increasing longevity: cutting calories.
Using a computerized test that scanned more than 6,000 genes at once, researchers analyzed muscle tissue from mice and found that only about 100 genes were changed substantially in elderly animals. A lifetime of restricted calories prevented changes in 80% of those genes, the researchers said. The finding greatly narrows the search for the genetic and biochemical mechanisms that forestall the ravages of time in animals on a restricted diet.
In the long run, the findings may help researchers pinpoint nutrients or drugs that accomplish in people the same life-extending, youth-preserving feat that chronic calorie deprivation confers on rodents.
Scientists have long observed that lab rodents that eat a diet containing sufficient nutrients but 30% to 50% fewer calories than normal live about one-third longer than usual and also appear younger, more vigorous and less prone to diseases like cancer.
What those findings mean for people is a major unanswered question, though just asking it has no doubt ruined a few desserts. Scientists know a great deal about the hazards of human obesity, but for obvious reasons have not been able to directly study the health effects of restricting large numbers of people to a nutritionally balanced and yet calorie-reduced diet for decades.
The new study maps a way around that obstacle by identifying some potentially important biochemical changes that occur in mice on a low-cal diet for most of their adult lives--30 months for the breed used in the study. Because mice and people share a great deal of physiology, the researchers assume that some of the observed changes also occur in people.
“We may have made a step forward in our ability to screen for drugs that may be able to retard aspects of aging,” said Richard Weindruch, a professor of medicine at the University of Wisconsin in Madison and a coauthor of the study. It appears in the journal Science.
The research is the first to use the screening technology to probe age-related changes in the level of activity of specific genes, said Huber Warner, a research official at the National Institute on Aging, which provided funds for the study. Still, the technique is so new that other researchers will not be confident of the results until further tests are done, he said.
Raj Sohal, a professor of biological sciences at Southern Methodist University, said the study “breaks new ground in giving us an understanding of what happens to gene expression with age.”
In the study, the Wisconsin researchers fed three mice a normal diet, while three mice received 25% fewer calories beginning in adulthood, at about 5 months.
At 30 months--roughly equivalent to 80 human years--the researchers took muscle tissue from the normally fed and calorie-deprived mice and extracted genetic material from the cells. They then tested the activity of 6,347 genes using a GeneChip, produced by the Santa Clara biotech firm Affymetrix Inc.
A GeneChip is a glass slide that has the nucleic acid signatures of preselected genes robotically etched on its surface. When a biological sample containing one of the preselected genes is added to the slide, the gene binds with the signature. That causes a fluorescent reaction. The more active the gene, the more genetic material will be in the original sample and the more intense will be the light from the reaction.
Genes, which transmit genetic information from one generation to the next, also control body chemistry, though indirectly. They produce the proteins such as enzymes and hormones that take part in chemical reactions.
The Wisconsin researchers found that, compared to young adult mice, old mice on a normal diet had 55 genes that went substantially down in activity, while 58 genes went up. The changes reflected a wide range of biochemical responses. For instance, there was a rise in an enzyme that helps repair muscle tissue, seemingly reflecting the age-associated weakening of muscle fibers that is a familiar sign of growing old.
Significantly, the mice that were fed the restricted diet did not appear to have experienced most of the changes in gene activity endured by the normally fed mice. That indicates that those mice had undergone a “metabolic reprogramming,” as the Wisconsin researchers put it.
“We think the study provides a global view of changes in gene expression as caused by aging and its retardation by caloric restriction,” Weindruch said. “Most of the age-related changes we observed were prevented or reduced by caloric restriction.”
The approach, said coauthor Tomas Prolla, is “likely to have a major impact on the development of drugs or nutritional approaches to slowing down aging.”
Warner, of the aging institute, counseled restraint in interpreting the findings. But he also said he knew of three other research teams taking a similar approach, auguring a new era of research.
Public--and commercial--interest in reducing aging’s toll is considerable. The Wisconsin team has applied for a patent on the work, and Weindruch said his group was negotiating with a San Diego biotechnology firm, Mitos Inc., to expand the research.
