A new study from the NIA Intramural Research Program (IRP) suggests that mutations in mitochondrial DNA could give rise to age-related diseases. Mitochondria, which create energy to power our cells and bodies, contain their own DNA. IRP investigators sought to assess whether a specific type of mitochondrial DNA sequence known as a G-quadruplex could generate mutations in mitochondrial DNA. These G-quadruplexes, or G4s, are complex four-strand DNA structures which are hypothesized to interfere with normal DNA synthesis due to their bulky structure, potentially leading to DNA mutations. In order to test this hypothesis, the investigators first analyzed genomic data from two NIA-supported Italian studies, SardiNIA and InCHIANTI, and discovered that the G4 sequences contained a significant proportion of mitochondrial DNA mutations. Follow-up laboratory tests showed that G4 sequences create these mutations by halting normal DNA synthesis. Mitochondrial mutations, in turn, can disrupt normal cellular functioning and cause brain, nervous, cardiovascular, and muscular diseases, including those associated with aging. This study was published in Human Molecular Genetics.