Cracking the aging code: Study combines two competing theories to redefine anti-aging science

Scientists have long debated what makes our body clock tick, with two competing theories dominating the discussion. Now, research from the University of California, San Diego shows that these theories are not competitors after all—they are closely related and could fundamentally change the way we approach treatments for aging.

The groundbreaking study, published in the journal Nature Aging, analyzed genetic data from more than 9,000 human patients and revealed a previously unknown link between random DNA mutations and epigenetic modifications, which occur without changing the DNA sequence itself. conditions that affect chemical changes in the way genes are expressed.

“Major research institutions and companies are betting on reversing the epigenetic clock as a strategy to reverse the effects of aging, but our study suggests this may only treat the symptoms of aging rather than the root cause,” said Dr. Trey Ideker. ., professor at the University of California, San Diego School of Medicine and study co-author.

When examining data from The Cancer Genome Atlas and other genomic repositories, researchers found that a single genetic mutation can trigger a cascade of epigenetic changes throughout the genome, well beyond the site of the mutation. This one-to-many relationship helps explain how relatively rare mutations can lead to widespread epigenetic changes during aging.

“If mutations are indeed responsible for the observed epigenetic changes, then this fact could fundamentally change the way we approach anti-aging efforts in the future,” explains Edek.

The findings reconcile two seemingly independent processes: random DNA damage that accumulates over time, and the more predictable epigenetic modifications that scientists use to measure biological age. These epigenetic changes are particularly attractive to researchers because, unlike mutations, they have the potential to be reversed.

“If somatic mutations are the fundamental drivers of aging, and epigenetic changes merely track the process, then reversing aging will be much more difficult than we previously thought,” said co-corresponding author Steven M. of the University of California, San Francisco. Cummings, MD, noted. “This shifts our focus from viewing aging as a programmed process to one that is largely influenced by random, cumulative changes over time.”

The study analyzed data from 9,331 patients, focusing on how genetic mutations are associated with changes in DNA methylation, a specific type of epigenetic modification. The researchers found that they could predict an individual’s age with similar accuracy using mutation patterns or epigenetic changes, suggesting that both were measuring the same underlying aging process.

“Epigenetic clocks have been around for many years, but we are only now beginning to answer the question of why epigenetic clocks operate in the first place,” explains first author Zane Koch, a Ph.D. candidate at UC San Diego. “Our study is the first to demonstrate that epigenetic changes are intricately and predictably associated with random genetic mutations.”

These findings have important implications for current anti-aging research, much of which focuses on reversing epigenetic changes. If these changes are primarily the result of irreversible DNA mutations rather than an independent cause of aging, then these approaches may need to be reconsidered.

While the team acknowledges that more research is needed to fully understand the relationship between mutations and epigenetic changes during aging, their findings provide important insights into the fundamental mechanisms by which we age at the molecular level.