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Dec 4, 2007

Researchers Discover that Overexpression of a Protein Prevents Some Age-Related Disorders

  • Investigators at Washington University School of Medicine in St. Louis found that activating a protein in mice muscle tissue increases average lifespan and prevents some diseases. They caution, though, that it does not extend maximum lifespan.

    Past research found that mice with extra uncoupling protein-1 in muscle tissue are protected from diabetes and obesity. In the current experiments, the Washington Univ. team bred large numbers of mice, fed them a normal chow diet, and followed each mouse until its natural death. Half were genetically engineered to overexpress a uncoupling protein-1. In muscle tissue,  this protein converts the energy from food into heat and mimics the effects of exercise.

    The animals that lived the longest in each group survived for 39 months and died within two weeks of one another. What was different was the median lifespan for the mice. Median survival in the uncoupled mice was 30 months, compared to 27 months for their wild-type littermates.

    The scientists also found that decreasing body fat and inflammation in the animals by accelerating muscle metabolism with uncoupling protein also delayed diseases including atherosclerosis, diabetes, hypertension, and even cancer.

    The researchers examined the mice after each animal died. They discovered that the female mice with the uncoupling protein mutation were less likely to develop lymphoma. No differences in lymphoma rates were found in male mice. Increased expression of uncoupling protein-1 also reduced markers of chronic inflammation. In a second set of experiments, the researchers found that the uncoupled mice were less likely to have vascular disease.

    The team also generated a line of mice, already prone to obesity, that also made extra uncoupling protein only after the animals received drug therapy. When the researchers gave these animals an antibiotic drug, they manufactured more uncoupling protein in muscle tissue and reversed their problems with glucose metabolism and hypertension.

    The findings are published in the December issue of Cell Metabolism.



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