Discover how epigenetic clocks, which measure DNA methylation, are revolutionising our understanding of biological aging and disease prediction, offering new insights into cellular processes.
Key Points
- Epigenetic clocks estimate biological age by measuring DNA methylation, affecting gene activity.
- Different epigenetic clocks capture distinct aspects of aging, such as immune system changes and metabolism.
- Researchers developed new gene-expression-based clocks with enhanced predictive power for age-related diseases and mortality.
- The study analysed five widely used epigenetic clocks, revealing their specific biological pathways.
- Common themes across clocks include changes in the immune system, metabolism, and cell communication, all linked to aging.
Epigenetic clocks, which help estimate one's biological age, function by capturing different aspects of the biology of aging, such as changes in the immune system, metabolism and cell communication, a recent study has found.
Epigenetic clocks are tools measuring a chemical change called DNA methylation, which doesn't change the genetic code, but affects which genes are turned 'off' or 'on'. The chemical changes on top of the base DNA are collectively called the epigenome.
Understanding Epigenetic Clocks And Biological Age
Findings published in the journal npj Aging shows the variability in what five of the most widely used epigenetic clocks -- Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE -- are actually measuring.
Researchers, including those from the University of Southern California, US, also developed new gene-expression-based clocks to complement existing epigenetic clocks, which they said show an even stronger predictive power for age-related disease and mortality.
"Aging isn't just about the number of candles on your birthday cake -- it's also about what's happening inside your cells," lead author Thalida Em Arpawong, research associate professor of gerontology at the University of Southern California, said.
"We found that different clocks capture different aspects of the biology of aging and developed new transcriptomic aging gene scores that complement existing clocks and, in some cases, better predict age-related disease and mortality," Arpawong said.
New Gene-Expression Clocks Enhance Prediction
The researchers studied blood samples from 3,227 participants in the Health and Retirement Study in the US.
They compared DNA methylation patterns with gene expression, or how often genes are transcribed from DNA into RNA and used to make proteins. All of the transcription taking place within a cell at a given time is referred to as the transcriptome.
The team examined the combined epigenetic and transcriptomic measurements to compare gene expression and identify the biological pathways highlighted by each of five epigenetic clocks.
Distinct Biological Pathways Of Aging
Each aging clock was associated with different biological processes, from energy balance and cellular growth to immune cell activation and inflammatory signalling.
While the clocks emphasised varied biological pathways, they shared several common themes, including changes in the immune system, metabolism and cell communication -- all well-known features of aging, the researchers said.
"Each clock also showed distinct signatures: Horvath was enriched for metabolism and signal transduction; Hannum for homeostasis and vascular wall interactions; GrimAge for Interferon signalling; PhenoAge for activated cellular senescence and mitotic pathways alongside repression of transcriptional and viral interaction pathways," the authors wrote.
"DunedinPACE exhibited the most extensive profile, with activation of pathways spanning protein metabolism, immune signalling, nervous system development, and cellular respiration, and repression of pathways related to DNA repair, G protein-coupled receptor signalling, ECM organisation, and neuronal processes," they said.
