NEW YORK (Reuters Health) - Providing clues on why we all must eventually gray and wrinkle, new research in mice supports the theory that damage to the body's DNA is responsible for aging.

Researchers in the Netherlands found that mice with a defect in a gene involved in DNA repair aged prematurely, developing brittle bones, gray fur, infertility and other hallmarks of old age. Mice that carried an additional defect in the gene, known as XPD, showed greatly accelerated aging, along with greater sensitivity to oxidative damage to DNA.

Jan de Boer of Erasmus University in Rotterdam and colleagues reported their findings Thursday in Sciencexpress, the online edition of the journal Science.

DNA damage has long been thought to contribute to aging, but the exact mechanisms remain unclear. Among the factors that can harm DNA are reactive oxygen species, cell-damaging forms of oxygen that are byproducts of normal metabolism and that are believed to contribute to diseases such as heart disease and cancer.

Environmental insults that can harm DNA--and potentially lead to cancer--include overexposure to the sun's UV rays and certain chemicals, such as those in cigarette smoke, de Boer noted.

Now this study, he told Reuters Health, "provides the first clear indication that DNA damage is at the root of aging."

The mice in the study were engineered to have a gene mutation found in people with the disease trichothiodystrophy (TDD), a genetic disorder marked by features like brittle hair, stunted growth and skin sensitivity to light. The defective gene, XPD, is involved in transcribing instructions from DNA to make proteins and in repairing DNA damage.

The investigators found that mice with the mutant gene developed normally but aged quickly once they reached adulthood. In addition, mice with the double-mutation in the gene were "hypersensitive" to oxidative stress, according to the researchers.

De Boer explained that the defect in DNA repair in these mice meant that genetic damage was allowed to accumulate, causing dysfunction and accelerated death rates in cells--culminating in the rapid aging of the animal.

These findings, de Boer said, "strongly suggest that normal aging is also due to DNA damage."

They also point to some familiar anti-aging tactics, the researcher noted. Protecting the skin from UV rays and not smoking are two well-known measures.

Preventing oxidative stress--a natural consequence of metabolism--is another matter, de Boer said. However, he added, a healthful diet rich in antioxidants might help "to some extent."

Antioxidants, which include vitamins C, E and beta-carotene and compounds such as lycopene and lutein, help neutralize reactive oxygen species.

De Boer noted that there is also evidence from animal research that a low-calorie lifestyle can extend the life span.

The mouse study does support the theory that "wear and tear on the DNA" is the basis for aging, according to an accompanying editorial by Paul Hasty and Jan Vijg of University of Texas Health Science Center in San Antonio.

However, the editorialists add, the "true nature of the premature aging phenomenon" in these genetically altered mice is still not completely understood.

SOURCE: Sciencexpress 2002;10.1126/science.1070174.

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