US scientists have examined the biological processes behind five widely used ageing tests, finding that different methods appear to capture different aspects of how the human body ages.
Researchers analysed blood samples from 3,227 people who took part in the US Health and Retirement Study. They compared five commonly used epigenetic clocks with patterns of gene activity in the participants’ blood to determine what biological changes were associated with faster ageing according to each test.
Epigenetic clocks are mathematical tools that estimate biological age using DNA methylation, chemical changes that can influence how genes function without altering the underlying genetic code.
Scientists have increasingly used these clocks to investigate links between biological ageing, disease, physical decline and the risk of death. However, researchers have not always known precisely what processes inside the body were being reflected when a clock indicated that someone was ageing faster than expected.
The new study found that the five clocks were associated with different molecular signs of ageing. Some were more strongly connected to processes involved in energy use and cell growth, while others showed stronger links to immune activity and inflammation.
Despite those differences, the clocks shared several biological features. These included changes involving the immune system, metabolism and communication between cells.
The findings could help researchers select the most appropriate biological ageing test for a particular study. A clock associated more closely with immune activity, for example, could be more useful for research into immune-related ageing than one that primarily reflects metabolic changes.
The researchers also developed new measures called transcriptomic ageing gene scores, or TAGS, based on the molecular patterns identified in their analysis.
According to the study, TAGS in several cases performed better than the ageing clocks alone when predicting health outcomes. These included frailty, walking speed, heart disease, diabetes, lung disease and mortality.
T. Em Arpawong, a research associate professor at the USC Leonard Davis School of Gerontology, said ageing is not determined simply by chronological age but also by biological changes taking place inside cells.
Senior author Eileen Crimmins said the study helps explain what is happening beneath the surface when biological ageing tests produce their results.
By identifying the molecular processes associated with individual ageing clocks, researchers may be able to interpret their readings more accurately and understand which tools are best suited to different areas of ageing research.
The findings could eventually support research into preventing age-related illness and identifying people at higher risk of declining health. However, the study focuses on biological markers and does not mean the new measures are ready to replace clinical assessments of health or provide individual predictions of lifespan.
Researchers said the work provides a clearer picture of the biological mechanisms captured by ageing clocks and could guide their use in future studies of ageing and disease.
