How old are you really? Study explains what makes 'epigenetic clocks' tick, debuts new prediction tools
What do "epigenetic clocks" actually measure? These lab tests have become popular tools for studying biological aging, or how the body's cellular function changes at a faster or slower rate than expected. However, the underlying biology behind each of these measurements has remained largely unknown until now.
Scientists have long known that humans age at varying rates biologically, with some individuals appearing much younger or older than their actual age on paper. To quantify this difference, researchers employ epigenetic clocks, which estimate biological age by measuring a chemical alteration called DNA methylation. However, the biological mechanisms behind these clocks remained unclear until now.
A recent study led by the USC Leonard Davis School of Gerontology, published in npj Aging, has unveiled how epigenetic clocks work and developed new gene expression-based tools that may predict age-related disease and mortality more accurately than existing clocks.
DNA methylation is a chemical change that occurs on top of a person's genetic code but affects which genes are turned on or off. This change, part of the epigenome, can predict health issues and death risk better than chronological age alone. The study analyzed blood samples from 3,227 U.S. adults and compared DNA methylation patterns with gene expression—the frequency of gene transcription from DNA into RNA and protein production.
By examining combined epigenetic and transcriptomic measurements, the researchers discovered that each of the five widely used epigenetic clocks measured different aspects of biological aging, such as energy balance, cellular growth, immune cell activation, and inflammatory signaling.
Despite emphasizing different biological pathways, the clocks shared several common themes, including changes in the immune system, metabolism, and cell communication. To complement the existing epigenetic clocks, the scientists created new tools called transcriptomic aging gene scores (TAGS), which provide a clearer picture of a person's biological health.
TAGS have demonstrated even stronger predictive power for health outcomes like frailty, walking speed, heart disease, diabetes, lung disease, and mortality compared to the epigenetic clocks alone. The findings can help researchers select the most suitable aging clock for specific studies, offering insights into the underlying biology of aging and bringing scientists closer to utilizing these measures to predict disease, track healthy aging, and guide medical care.
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