A new study is raising questions about whether a suspect fingered by scientists is as big a driver of human aging as previously thought. For years, researchers believed that small DNA mutations in the energy-producing parts of our cells lead us down the road to aching bodies and wrinkled skin. But mice engineered to have hundreds of times more of these mutations than average showed no signs of premature aging, indicating that scientists are going to have to look elsewhere for their culprit.
Cells contain thousands of tiny structures called mitochondria, which generate energy and harbor their own DNA distinct from the cell's nucleus. Scientists suspect this DNA, called mitochondrial DNA, or mtDNA, may be more vulnerable to mutations from errors in DNA replication. Over the last five years, several studies in mice pointed to a link between these mutations in mtDNA and the decline of tissue function that occurs as humans and animals age.
To see whether point mutations, which affect just one DNA base in mtDNA, are directly involved in aging, a team of researchers at the University of Washington in Seattle charted mtDNA mutation frequency in normal mice and "mitochondrial mutator" mice. The mutator mice were engineered to have 500 times more mtDNA mutations than their normal counterparts. Nevertheless, the mutator mice showed no signs of premature aging, such as osteoporosis, balding, or reduced fertility, the team reported online 4 March in Nature Genetics. "This suggests that point mutations [in mtDNA] aren't involved in aging-related pathology," says Marc Vermulst, the study's lead author and a doctoral student in the lab of cancer research scientist Lawrence Loeb.
This claim may be a bit premature, however, cautions Jan Vijg, a molecular geneticist at the Buck Institute, a nonprofit research center in Novato, California. Point mutations are tissue-specific, he says, meaning that some tissues may be more prone to mtDNA mutations than others. Vermulst's study looked only at tissues from the heart, brain, and embryonic fibroblasts. In addition, says Vijg, the mutator mouse Loeb used may not be the best model for these studies. Mutations in these animals began to amass during embryonic development, while normal animals don't begin to accumulate mutations until after birth.