Building on their groundbreaking analysis in epigenetics and transposable components associated to growing old, scientists at Eötvös Loránd University have achieved a important breakthrough in unraveling the molecular mechanisms of growing old.
Drs. Ádám Sturm and Tibor Vellai of Eötvös Loránd University have achieved one other important breakthrough within the research of growing old, increasing on their groundbreaking analysis into the epigenetics of growing old and transposable components. These new findings have deepened our understanding of the molecular mechanisms behind growing old.
Their newest research, printed within the International Journal of Molecular Sciences, reveals a novel epigenetic mechanism in mitochondrial DNA (mtDNA) that would revolutionize our method to growing old analysis and diagnostics.
In their earlier landmark articles, “The mechanism of aging: primary role of transposable elements in genome disintegration” (2015) and “Downregulation of transposable elements extends lifespan in Caenorhabditis elegans” (2023), Dr. Sturm and Dr. Vellai established the essential function of transposable components within the growing old course of. Their present analysis expands on this basis, uncovering a new layer of complexity in mobile growing old.
Discovery of the Mitochondrial Epigenetic Clock
The analysis staff has found that a beforehand hidden DNA modification, N6-methyladenine (6mA), that progressively accumulates in mtDNA as organisms age. This phenomenon was noticed throughout various species, together with the nematode Caenorhabditis elegans, the fruit flyDrosophila melanogaster, and canine, suggesting an evolutionary conserved mechanism within the growing old course of throughout all animal species.
“We’ve discovered what could be described as a ‘mitochondrial epigenetic clock,” explains Dr. Sturm. “This clock ticks at different rates depending on the lifespan of the organism, providing a new perspective on how aging is regulated at the cellular level. It’s fascinating to see how this connects to our earlier work on transposable elements and genome stability.”
To resolve earlier disputes concerning the existence of the hidden 6mA modification mark in animal genomes, the staff developed a novel, dependable PCR-based technique for detecting these modifications. This approach permits for correct, sequence-specific measurement of 6mA ranges in mtDNA, overcoming the constraints of earlier strategies.
Linking 6mA Accumulation to Longevity
A key discovering of the research was that long-lived C. elegans mutants, which dwell twice so long as wild-type worms, accumulate 6mA at half the speed of their regular counterparts. This commentary strongly hyperlinks the speed of 6mA accumulation to the growing old course of and lifespan regulation, harking back to the staff’s earlier findings on transposable component exercise and longevity.
The analysis additionally elucidated the enzymatic pathways accountable for including and eradicating 6mA modifications in mtDNA. Surprisingly, these look like the identical enzymes concerned in nuclear DNA methylation, suggesting a coordinated epigenetic regulation throughout totally different mobile compartments.
Dr. Vellai emphasizes the potential implications of this discovery: “Our findings open up new avenues for understanding and potentially intervening in the aging process. This epigenetic clock in mtDNA could serve as a more accessible and cost-effective way to measure biological age, compared to existing methods. When combined with our previous insights on transposable elements, we’re gaining a more comprehensive picture of the aging process.”
The research paves the best way for future analysis on how environmental elements, life-style decisions, and potential interventions may affect the speed of 6mA accumulation in mtDNA and transposable component exercise. Understanding these epigenetic modifications may result in novel methods for selling more healthy growing old and probably extending healthspan.
Reference: “N6-Methyladenine Progressively Accumulates in Mitochondrial DNA during Aging” by Ádám Sturm, Himani Sharma, Ferenc Bodnár, Maryam Aslam, Tibor Kovács, Ákos Németh, Bernadette Hotzi, Viktor Billes, Tímea Sigmond, Kitti Tátrai, Balázs Egyed, Blanka Téglás-Huszár, Gitta Schlosser, Nikolaos Charmpilas, Christina Ploumi, András Perczel, Nektarios Tavernarakis and Tibor Vellai, 2 October 2023, International Journal of Molecular Sciences.
DOI: 10.3390/ijms241914858
