Based on their groundbreaking research into epigenetics and transposable elements associated with aging, scientists at Etvesh Lorand University have achieved a major breakthrough in unraveling the molecular mechanisms of aging.

Dr. Adam Sturm and Tibor Vellai from the University of Etwes Lorand have made another major breakthrough in aging research by expanding their groundbreaking research to include epigenetics of aging and mutable elements. These new discoveries advance our understanding of the molecular mechanisms of aging.

Their most recent work was published on: International Journal of Molecular Sciences reveals a novel epigenetic mechanism in mitochondrial DNA (mtDNA) that could revolutionize our approach to aging research and diagnosis.

In their previous landmark papers, The Mechanism of Aging: The Essential Role of Transposable Elements in Genome Fragmentation (2015) and Downregulation of Transposable Elements Extends Lifespan in Caenorhabditis elegans (2023), Dr. Sturm and Dr. Vellai demonstrated the critical role of transposable elements in the genome during the aging process. Their current research expands on this foundation, revealing a new level of complexity in cellular aging.

Discovery of the mitochondrial epigenetic clock

The research team found that N6-methyladenine (6mA), a previously hidden DNA modification, progressively accumulates in mtDNA as organisms age. This phenomenon has been observed in a variety of species, including nematodes. Caenorhabditis elegansfruit fly Drosophila melanogaster and dogs, pointing to an evolutionarily conserved mechanism in the aging process of all animal species.

“We discovered what might be described as a ‘mitochondrial epigenetic clock,'” explains Dr. Sturm. “This clock ticks at different speeds depending on the organism’s lifespan, opening new insights into how aging is regulated at the cellular level. It’s exciting to see how this connects to our previous work on transposable elements and genome stability.”

To resolve previous debates about the existence of a hidden 6mA modification signature in animal genomes, the team developed a new, reliable PCR-based method to detect these modifications. This technique enables accurate sequence-dependent measurements of 6mA levels in mtDNA, overcoming the limitations of previous methods.

Durable 6mA battery pack

A key finding of the study was the longevity of the mutants. C. elegansWorms that lived twice as long as wild-type worms accumulated half as much 6 mA as normal worms. This observation closely links the rate of 6 mA accumulation to the aging process and lifespan regulation, echoing the team’s previous findings on transporter activity and longevity.

The study also elucidated the enzymatic pathways responsible for the addition and removal of 6mA modifications in mtDNA. Surprisingly, these are the same enzymes involved in nuclear DNA methylation, suggesting coordinated epigenetic regulation in different cellular compartments.

Dr. Vellai highlights the potential implications of this discovery: “Our findings open new avenues for understanding and potentially intervening in the aging process. This epigenetic clock in mtDNA may serve as a more accessible and cost-effective way to measure biological age compared to current methods. Combined with our previous knowledge of the elements that change, we obtain a more complete picture of the aging process.”

The study paves the way for future studies on how environmental factors, lifestyle choices, and potential interventions may influence the rate of 6mA accumulation and the activity of transposable elements in mtDNA. Understanding these epigenetic changes could lead to new strategies to promote healthier aging and potentially extend healthspan.