Genetic Manipulation Extends Life of Mice 20%

But Translating Findings to Humans Faces Many Hurdles

By reducing the activity of one type of gene, scientists said they increased the average life span of mice by about 20%, a feat that in human terms is akin to extending life by about 15 years.

Moreover, the researchers at the National Institutes of Health found that memory, cognition and some other important traits were better preserved in the mice as they aged, compared with a control group of mice that had normal levels of a protein put out by the gene.

By manipulating a single gene, scientists at the National Institutes of Health said they increased the average life span of mice by about 20%, a feat that in human terms is akin to extending life to about 90 years from 75. Ron Winslow reports. Photo: Getty Images.

The findings, published Thursday in the journal Cell Reports, strengthen the case that the gene, called mTOR, is a major regulator of the aging process.

The mice were bred to put out just 25% of the normal levels of mTOR protein, indicating that suppressing the activity of the gene “clearly makes mice live longer,” said Toren Finkel, head of the laboratory of molecular biology in NIH’s National Heart, Lung and Blood Institute and senior author of the new study.

Though mouse studies don’t always translate to humans, Dr. Finkel and other researchers said the results raise the possibility that targeting the gene with drugs that inhibit its activity might one day be at least part of a strategy for prolonging longevity in people.

Such a drug, an immunosuppressant called rapamycin, and some similar agents already are on the market and used to treat certain diseases, but researchers cautioned against taking such medicines, which have side effects, for anything but approved uses.

NIH/NHLBINIH researchers found that lowering the expression of a single gene helped extend the life of mice by about 20%. A mouse with a manipulated gene on the left and an unchanged mouse on the right.

The results also build on a growing body of research challenging the belief that aging is an intractable biological process, prompting scientists to think of slowing aging as a possible way to prevent disease.

“What we need right now is for scientists and the public to wake up to the concept that you can slow aging,” said Brian Kennedy, president of the Buck Institute for Aging Research in Novato, Calif., who wasn’t involved in the new study. “If you do, you prevent many of the diseases that we’re so scared of and that are associated with aging.” They include cardiovascular disease, cancer and Alzheimer’s disease.

Major hurdles stand in the path of translating the findings to humans, including whether inhibiting the action of mTOR would have similar life-extending effects, and if it did whether the benefit would come without unwanted problems.

The mice in the study had softer bones, developed more infections—probably from a depressed immune system—and may have had a higher risk of cataracts than normal mice, the researchers found. But they were also significantly less likely to develop cancer, Dr. Finkel said.

The mTOR gene has a well-established role in the metabolism and energy balance of cells, and researchers believe it is associated with the concept of caloric restriction. It has been known for about a century that animals that eat less live longer.

When there are a lot of calories present in cells, mTOR activity is turned up, “signaling the cell to grow and divide,” Dr. Kennedy said. “If there are fewer calories, the pathway is turned down and that signals the cell to stop proliferating and become stress resistant.” That helps animals live longer, he said.

The name mTOR stands for mechanistic target of rapamycin, a drug used in certain treatments for cancer and heart disease and also to suppress the immune system to prevent rejection of organ transplants.

“It’s early days to suggest that rapamycin is something that people would want to take” to increase longevity,” said David Sabatini, professor of biology at the Massachusetts Institute of Technology and the Whitehead Institute for Biomedical Research in Cambridge, Mass., who wasn’t involved in Thursday’s study. “But [research] is clearly hinting at a pathway that matters.”

In the study, Dr. Finkel found that the median life span for the mTOR-deficient mice was 28 months for males and 31.5 months for females, compared with the span for normal mice of 22.9 months for males and 26.5 months for females.


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