Sturm, , Sharma, H., Bodnár, F., Aslam, M., Kovács, T., Németh, , Hotzi, B., Billes, V., Sigmond, T., Tátrai, K., Egyed, B., Téglás-Huszár, B., Schlosser, G., Charmpilas, N., Ploumi, C., Perczel, A., Tavernarakis, N., Vellai, T. (2023). N[6]-Methyladenine Progressively Accumulates in Mitochondrial DNA during Aging.  Int. J. Mol. Sci. 24(19): 14858.

FBrf0257835

Research paper

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.

PMC10573865 (PMC) (EuropePMC)