The mitochondrial DNA of C57BL/6 (BL/6) mice and NZB/OlaHsd (NZB) mice has a degree of divergence comparable to that of the mitochondrial DNA of Eurasian and African humans. In Nature, Enriquez and colleagues show that BL/6NZB mice, which have a BL/6 nuclear genome and NZB mitochondrial DNA, have an extended median lifespan, fewer signs of aging and a lower telomere-length-reduction rate relative to that of BL/6 mice. BL/6NZB mice have higher expression of factors involved in lipid metabolism and lower expression of those factors involved in inflammatory pathways, better preservation of mitochondrial respiration, respiratory complexes and ATP synthesis, and lower old-age production of mitochondrial reactive oxygen species than that of BL/6 mice. 1-year-old BL/6NZB mice have a greater ability to regulate glucose and insulin concentrations during fasting or when fed a high-fat diet. These metabolic 'readouts' correlate with a more active regulation of the mitochondrial proteome and less mitochondrial fragmentation in the heart and liver of BL/6NZB mice relative to that of BL/6 mice.

Nature (6 July 2016) doi:10.1038/nature18618