학술논문
N 6 -Methyladenine Progressively Accumulates in Mitochondrial DNA during Aging.
Document Type
Article
Author
Sturm, Ádám; Sharma, Himani; Bodnár, Ferenc; Aslam, Maryam; Kovács, Tibor; Németh, Ákos; Hotzi, Bernadette; Billes, Viktor; Sigmond, Tímea; Tátrai, Kitti; Egyed, Balázs; Téglás-Huszár, Blanka; Schlosser, Gitta; Charmpilas, Nikolaos; Ploumi, Christina; Perczel, András; Tavernarakis, Nektarios; Vellai, Tibor
Source
Subject
*MITOCHONDRIAL DNA
*SOMATOMEDIN
*DROSOPHILA melanogaster
*CAENORHABDITIS elegans
*AGING
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Language
ISSN
1661-6596
Abstract
N6-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 N6-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 N6-adenine methylation in aging and reveal an efficient diagnostic technique to determine age using DNA. [ABSTRACT FROM AUTHOR]