N6-Methyladenine Progressively Accumulates in Mitochondrial DNA during Aging

N-6-methyladenine (6mA) in the DNA is a conserved epigenetic mark with various cellular, physiological and developmental functions. Although the presence of 6mA was discovered a few years ago in the nuclear genome of distantly related animal taxa and just recently in mammalian mitochondrial DNA (mtDNA), accumulating evidence at present seriously questions the presence of N-6-adenine methylation in these genetic systems, attributing it to methodological errors. In this paper, we present a reliable, PCR-based method to determine accurately the relative 6mA levels in the mtDNA of Caenorhabditis elegans, Drosophila melanogaster and dogs, and show that these levels gradually increase with age. Furthermore, daf-2(-)-mutant worms, which are defective for insulin/IGF-1 (insulin-like growth factor) signaling and live twice as long as the wild type, display a half rate at which 6mA progressively accumulates in the mtDNA as compared to normal values. Together, these results suggest a fundamental role for mtDNA N-6-adenine methylation in aging and reveal an efficient diagnostic technique to determine age using DNA.

Automated summary

Researchers present a reliable PCR-based method to accurately determine the levels of 6mA in mtDNA of Caenorhabditis elegans, Drosophila melanogaster, and dogs, and show that these levels increase with age. Furthermore, mutant worms with defective insulin/IGF-1 signaling display a slower rate of 6mA accumulation in mtDNA compared to normal values.