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Understanding the pace at which people age has long intrigued scientists, as various behavioral and lifestyle factors can either accelerate or slow down this process. These factors—ranging from chronic stress and poor nutrition to smoking and alcohol consumption—leave lasting imprints on our genome in the form of epigenetic marks. By analyzing these marks, researchers can estimate an individual's biological age and their risk for age-related diseases. Epigenetic clocks have become an important tool in this area, allowing scientists to predict how well a person is aging relative to their chronological age.
A recent study published in Frontiers in Aging introduces a novel approach to measuring biological age. Researchers developed an epigenetic clock called CheekAge, which uses DNA methylation data from cells collected through a simple cheek swab, offering a less invasive alternative to traditional blood-based methods. The study demonstrates that CheekAge can not only predict a person’s biological age but also estimate their risk of mortality—even when methylation data from different tissues, such as blood cells, is used.
“We also demonstrate that specific methylation sites are especially important for this correlation, revealing potential links between specific genes and processes and human mortality captured by our clock,” said Maxim Shokhirev, the study’s first author and Head of Computational Biology and Data Science at Tally Health.
Cheek Cells as a New Source for Aging Analysis
Most first-generation epigenetic clocks relied on blood samples, which can be difficult and stressful to collect. However, CheekAge provides a more convenient option, using cells from the inside of the cheek to assess DNA methylation. This new clock was trained by correlating methylation levels at approximately 200,000 genomic sites with scores that reflect health and lifestyle factors. By using this approach, researchers can estimate physiological aging more easily.
In this study, the team evaluated how well CheekAge predicted mortality in a cohort of 1,513 individuals born in 1921 and 1936. These participants were part of the Lothian Birth Cohorts (LBC) study at the University of Edinburgh, which tracks cognitive aging, lifestyle, and various biomedical and genetic factors. Every three years, participants’ blood methylomes were measured across roughly 450,000 DNA methylation sites, and the data was then analyzed in relation to their mortality status, which was obtained from the Scottish National Health Service Central Register.
The researchers found that CheekAge outperformed earlier clocks that relied on blood data alone. “CheekAge is significantly associated with mortality in a longitudinal dataset and outcompetes first-generation clocks trained in datasets containing blood data,” concluded the authors.
Strong Links Between CheekAge and Mortality Risk
CheekAge showed a strong correlation with all-cause mortality, especially in older adults. Specifically, for every one standard deviation increase in CheekAge, the hazard ratio for mortality increased by 21%. This suggests that CheekAge can be a reliable predictor of mortality risk.
“The fact that our epigenetic clock trained on cheek cells predicts mortality when measuring the methylome in blood cells suggests there are common mortality signals across tissues,” said Shokhirev. “This implies that a simple, non-invasive cheek swab can be a valuable alternative for studying and tracking the biology of aging.”
Identifying Key Genetic Links to Mortality
To further explore the utility of CheekAge, the researchers analyzed specific methylation sites that were most strongly associated with mortality. Genes located near these sites could provide valuable clues about factors that influence lifespan and the risk of age-related diseases. For instance, the gene PDZRN4, a possible tumor suppressor, and ALPK2, a gene involved in cancer and heart health, stood out in the analysis. Other genes were linked to conditions such as cancer, osteoporosis, inflammation, and metabolic syndrome.
“It would be intriguing to determine if genes like ALPK2 impact lifespan or health in animal models,” said Adiv Johnson, the study’s last author and Head of Scientific Affairs and Education at Tally Health.
While this study focused on mortality risk, future research may explore whether CheekAge can predict other outcomes, such as the incidence of specific age-related diseases or the duration of a person’s health span—the period of life free from chronic diseases and disabilities. “Future studies are also needed to identify what other associations besides all-cause mortality can be captured with CheekAge,” Johnson added.
Publication Details
Shokhirev, M. N., Kramer, D. J., Corley, J., Cox, S. R., Cuellar, T. L., & Johnson, A. A. CheekAge, a next-generation epigenetic buccal clock, is predictive of mortality in human blood. Frontiers in Aging, 5, 1460360. https://doi.org/10.3389/fragi.2024.1460360
A recent study published in Frontiers in Aging introduces a novel approach to measuring biological age. Researchers developed an epigenetic clock called CheekAge, which uses DNA methylation data from cells collected through a simple cheek swab, offering a less invasive alternative to traditional blood-based methods. The study demonstrates that CheekAge can not only predict a person’s biological age but also estimate their risk of mortality—even when methylation data from different tissues, such as blood cells, is used.
“We also demonstrate that specific methylation sites are especially important for this correlation, revealing potential links between specific genes and processes and human mortality captured by our clock,” said Maxim Shokhirev, the study’s first author and Head of Computational Biology and Data Science at Tally Health.
Cheek Cells as a New Source for Aging Analysis
Most first-generation epigenetic clocks relied on blood samples, which can be difficult and stressful to collect. However, CheekAge provides a more convenient option, using cells from the inside of the cheek to assess DNA methylation. This new clock was trained by correlating methylation levels at approximately 200,000 genomic sites with scores that reflect health and lifestyle factors. By using this approach, researchers can estimate physiological aging more easily.
In this study, the team evaluated how well CheekAge predicted mortality in a cohort of 1,513 individuals born in 1921 and 1936. These participants were part of the Lothian Birth Cohorts (LBC) study at the University of Edinburgh, which tracks cognitive aging, lifestyle, and various biomedical and genetic factors. Every three years, participants’ blood methylomes were measured across roughly 450,000 DNA methylation sites, and the data was then analyzed in relation to their mortality status, which was obtained from the Scottish National Health Service Central Register.
The researchers found that CheekAge outperformed earlier clocks that relied on blood data alone. “CheekAge is significantly associated with mortality in a longitudinal dataset and outcompetes first-generation clocks trained in datasets containing blood data,” concluded the authors.
Strong Links Between CheekAge and Mortality Risk
CheekAge showed a strong correlation with all-cause mortality, especially in older adults. Specifically, for every one standard deviation increase in CheekAge, the hazard ratio for mortality increased by 21%. This suggests that CheekAge can be a reliable predictor of mortality risk.
“The fact that our epigenetic clock trained on cheek cells predicts mortality when measuring the methylome in blood cells suggests there are common mortality signals across tissues,” said Shokhirev. “This implies that a simple, non-invasive cheek swab can be a valuable alternative for studying and tracking the biology of aging.”
Identifying Key Genetic Links to Mortality
To further explore the utility of CheekAge, the researchers analyzed specific methylation sites that were most strongly associated with mortality. Genes located near these sites could provide valuable clues about factors that influence lifespan and the risk of age-related diseases. For instance, the gene PDZRN4, a possible tumor suppressor, and ALPK2, a gene involved in cancer and heart health, stood out in the analysis. Other genes were linked to conditions such as cancer, osteoporosis, inflammation, and metabolic syndrome.
“It would be intriguing to determine if genes like ALPK2 impact lifespan or health in animal models,” said Adiv Johnson, the study’s last author and Head of Scientific Affairs and Education at Tally Health.
While this study focused on mortality risk, future research may explore whether CheekAge can predict other outcomes, such as the incidence of specific age-related diseases or the duration of a person’s health span—the period of life free from chronic diseases and disabilities. “Future studies are also needed to identify what other associations besides all-cause mortality can be captured with CheekAge,” Johnson added.
Publication Details
Shokhirev, M. N., Kramer, D. J., Corley, J., Cox, S. R., Cuellar, T. L., & Johnson, A. A. CheekAge, a next-generation epigenetic buccal clock, is predictive of mortality in human blood. Frontiers in Aging, 5, 1460360. https://doi.org/10.3389/fragi.2024.1460360