A new study from the University of California San Diego School of Medicine has offered fresh insights into the intricate workings of the biological clock, reshaping our understanding of ageing at the molecular level. Published in Nature Aging, the research bridges two major theories of ageing: random genetic mutations and predictable epigenetic modifications. The latter, often referred to as the epigenetic clock, is widely used to measure biological ageing by tracking specific chemical changes in DNA.
However, the findings suggest that the biological clock may be more complex than previously thought. According to Dr Trey Ideker, co-author and professor at UC San Diego, efforts to “turn back” the epigenetic clock might only address symptoms of ageing rather than its root cause. “If mutations are responsible for epigenetic changes, this could transform anti-ageing strategies,” he noted.
The study explored two leading hypotheses. The somatic mutation theory suggests that ageing stems from the gradual accumulation of random DNA mutations. Meanwhile, the epigenetic clock theory attributes ageing to predictable epigenetic modifications, which alter gene activity without changing the DNA sequence. These modifications, unlike mutations, can sometimes be reversed, making them a popular target for anti-ageing research.
To investigate, researchers analysed data from over 9,000 patients, comparing genetic mutations with epigenetic changes. They discovered that mutations were closely linked to DNA methylation, a key epigenetic process. Remarkably, a single mutation could trigger widespread epigenetic alterations across the genome. This interplay allowed researchers to predict biological age using either mutations or epigenetic markers.
Lead author Zane Koch emphasised the significance of these findings: “We’re beginning to understand why the biological clock ticks, and our study shows a direct connection between mutations and epigenetic changes.”
While the research marks a breakthrough, further studies are needed to untangle the intricate relationship between these processes. As co-author Dr Steven Cummings pointed out, if mutations are the primary drivers of ageing, reversing the biological clock could be far more challenging than anticipated. This paradigm shift underscores the complexity of ageing and highlights the importance of continued exploration in the field.
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