Researchers at the University of California, San Diego, have published findings that shed light on a longstanding question: what causes molecular aging? Their study, published in Nature Aging, reveals an unprecedented link between two widely accepted explanations: random genetic mutations and predictable epigenetic modifications. The latter, known as the epigenetic clock theory, has been widely utilized by scientists as a consistent quantitative measure of biological aging.
However, the new research suggests that the process may not be so straightforward.
Leading research institutions and companies are investing in reversing the epigenetic clock as a strategy to counteract aging effects, but the study indicates that this may only address a symptom of aging rather than the underlying cause. If mutations are indeed responsible for the observed epigenetic changes, this could fundamentally alter the approach to anti-aging efforts in the future, according to Trey Ideker, Ph.D., corresponding co-author and professor at UC San Diego's School of Medicine and Jacobs School of Engineering.
There are two prevailing theories regarding the relationship between aging and DNA. The somatic mutation theory posits that aging results from the accumulation of mutations—permanent changes in our DNA sequence that occur randomly. The epigenetic clock theory suggests that aging occurs due to the accumulation of epigenetic modifications—minor changes in the chemical structure of DNA that do not alter the underlying sequence but change which genes are activated or deactivated. Unlike mutations, epigenetic modifications can, in some cases, be reversed.
Since epigenetic modifications occur only at specific sites in our genome rather than random locations, they are easier to quantify and have become a preferred method for scientists to determine the 'biological age' of cells. Nonetheless, the origin of these epigenetic changes has long been a question for scientists.
'Epigenetic clocks have existed for years, but we are just beginning to answer the question of why they work,' said Zane Koch, Ph.D. candidate in bioinformatics at UC San Diego and first author of the study. 'Our study demonstrates for the first time that epigenetic changes are intricately and predictably linked to random genetic mutations.'
The study's authors emphasize that further research is needed to fully understand the relationship between somatic mutations and epigenetic changes in aging. However, the findings represent a significant advancement in understanding the aging process and have important implications for developing new therapies aimed at preventing or reversing aging.
In addition to Ideker, Cummings, and Koch, the study was co-authored by Adam Li from UC San Diego and Daniel S. Evans from the California Pacific Medical Center Research Institute and UC San Francisco.