How mtDNA mutations cause aging

Mitochondrial DNA mutations appear to lead to aging by induced apoptosis and not by increased production of free radicals that lead to cellular damage as previously thought, scientists report in this week's Science. Tomas Prolla at the University of Wisconsin-Madison and colleagues found a rise in mtDNA mutations led to premature aging but not to increased levels of reactive oxygen species.

"The finding of no increased reactive oxygen species is very surprising," Nils-Goran Larsson at Karolinska University Hospital in Stockholm, Sweden, who did not participate in this study, told The Scientist. "The hypothesis that reactive oxygen species are important for aging must be reconsidered."

Prolla and colleagues created mice with a version of the mtDNA polymerase gamma that lacked proofreading capacity. These mutants showed premature aging, including hair loss, graying and hunched backs, and had a maximum life span of 460 days compared to more than 850 for wild-type mice. ...