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Elderly mice yield clues to the process of growing old

Delving deep into the molecular subtleties of a strain of mice engineered to age rapidly, scientists have found that an accumulation of genetic mutations prompts a cascade of programmed cell death that seems to underpin the aging process.

Writing today (July 15, 2005) in the journal Science, a team of scientists led by University of Wisconsin-Madison geneticist Tomas A. Prolla describes a series of experiments in mutant and normal mice that peel away some of the root secrets of mammalian aging.

Growing old, according to the new study, occurs, in part, as mutations build up in the DNA of energy-generating mitochondria, triggering the death of critical cells that lead to such things as hair and weight loss, hearing and vision impairment, loss of muscle mass, weakened bones and fewer circulating red blood cells. Mitochondria are structures within cells that provide energy for cells to move, divide, contract and secrete products vital for the health of organisms.

"We think that the key to what is happening in aging is that as (genetic) mutations or DNA damage accumulates, critical cells die," says Prolla. "These experiments favor a major role for programmed cell death in aging."

If true, the new insights may one day lead to opportunities to stave off old age through drugs that could prevent the gathering of genetic defects in mitochondrial DNA, genetic material that resides outside of the nucleus of a cell and that helps power critical cell processes.

Such insight could also lead to strategies to restore some functions such as hearing by protecting mitochondrial DNA from naturally occurring mutations.

Using mice genetically altered to have a deficiency in a protein that proofreads mitochondrial DNA and thus accumulate genetic mutations at a higher rate than unaltered mice, the group led by Prolla found evidence that programmed cell death, known as apoptosis, was greatly accelerated. The altered mice exhibited obvious hallma
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Source:University of Wisconsin-Madison


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