Mitochondrial DNA mutations and aging: devils in the details?

Although several lines of evidence support a role for accumulating somatic mitochondrial DNA (mtDNA) mutations in the etiology of aging, it remains unclear if they are a major cause of age-related deterioration and death. Mouse models that harbor elevated mtDNA mutation frequencies age prematurely; these findings were thought to provide conclusive evidence for a causal role of such mutations in aging. Yet, the presence of several conflicting reports has sparked controversy in the field and this is further aggravated by discrepancies in the estimates of mtDNA mutant fractions, which disagree by orders of magnitude. Here, we briefly review the evidence and some of the unresolved questions surrounding a causative role for accumulating mtDNA mutations in aging.