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Despite the search for the fountain of youth, growing older remains inevitable. Some biochemical effects of aging are thought to relate to cell structures called mitochondria, thousands of which are present in every cell. Mitochondria are the cell¿s energy converters and have their own DNA. Scientists have long known that mutations in mitochondrial DNA (mtDNA) become increasingly common in older animals, but they have not been able to determine whether such mutations are a cause of aging or an effect.
To answer this question, Aleksandra Trifunovic of the Karolinska Institute in Sweden and her colleagues genetically engineered a line of mice to carry a compromised version of an enzyme called DNA polymerase-gamma, which normally proofreads mitochondrial DNA to ensure proper replication and aids in DNA repair. Subsequent tests of the transgenic animals¿ brain, heart and liver cells revealed three to five times as many errors in their mtDNA as in that of normal mice. By 25 weeks of age, young adulthood for rodents, the mutants began to develop hallmark signs of aging, including heart problems, osteoporosis, baldness and reduced fertility. None of them lived more than 60 weeks, the researchers report today in Nature. Normal mice, in contrast, live 100 weeks on average. Future experiments can use the prematurely aging mice to study how growing old "can be counteracted by genetic, pharmacological, or dietary interventions," the team writes.
In an accompanying commentary, Lawrence A. Loeb and George M. Martin of the University of Washington in Seattle stress that the DNA polymerase-gamma is just one of several molecules that may be related to aging. Still, Loeb says, "this is the first noncorrelative evidence that mitochondrial mutations cause aging." With this knowledge in hand, he suggests, it may now be possible to engineer a mitochondrial polymerase with enhanced proofreading and repair abilities to see if such a molecule can prolong life. --Alla Katsnelson
