Similar to the Covid-19 PCR test, CheekAge requires a cheek swab to gather cell samples that will enable it to predict the risk of death for the person. — Filepic
We don’t all age at the same rate.
But while some supercentenarians may age exceptionally slowly due to winning the genetics jackpot, a plethora of behavioural and lifestyle factors are known to speed up ageing.
These include stress, poor sleep, poor nutrition, smoking and alcohol.
As such environmental effects get imprinted on our genome in the form of epigenetic marks, it is possible to quantify molecular ageing by characterising the epigenome at prognostic genomic sites.
Over the past decade, scientists have developed several such “epigenetic clocks”, calibrated against chronological age and various lifestyle factors across large numbers of people.
Most of these focused on DNA (deoxyribonucleic acid) methylation in blood cells, which makes collection of samples onerous, as well as stressful for the patient.
DNA methylation is a biological process that can change gene expression without changing the gene itself; it is strongly associated with ageing.
But earlier this year, scientists from the United States developed a second-generation clock, called CheekAge, which is based on methylation data in easy-to-collect cells from inside the cheeks.
Now, in the journal Frontiers in Aging, the team has shown for the first time that CheekAge can accurately predict the risk of mortality (death) – and even if epigenetic data from another tissue is used as input.
“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 Dr Maxim Shokhirev, the study’s first author and head of Computational Biology and Data Science at the company Tally Health in New York.
CheekAge was developed or “trained” by correlating the fraction of methylation at approximately 200,000 sites with an overall score for health and lifestyle, reflecting presumed differences in physiological ageing.
In the present study, Dr Shokhirev and colleagues used statistical programming to see how well it predicted mortality from any cause in 1,513 women and men, born between 1921 and 1936, and followed throughout life by the Lothian Birth Cohorts (LBC) programme of the University of Edinburgh in Scotland.
One of the LBC’s aims was to link differences in cognitive ageing to lifestyle and psychosocial factors, and biomedical, genetic, epigenetic and brain imaging data.
Every three years, the volunteers had their methylome in blood cells measured at approximately 450,000 DNA methylation sites.
The last available methylation time point was used along with the mortality status to calculate CheekAge and its association with mortality risk.
Data on mortality had been obtained from the Scottish National Health Service Central Register.
“[Our results show that] CheekAge is significantly associated with mortality in a longitudinal dataset and outcompetes first-generation clocks trained in datasets containing blood data,” concluded the authors.
Specifically, for every increase by a single standard deviation in CheekAge, the hazard ratio of all-cause mortality increased by 21%.
This means that CheekAge is strongly associated with mortality risk in older adults.
“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 Dr Shokhirev.
“This implies that a simple, non-invasive cheek swab can be a valuable alternative for studying and tracking the biology of ageing.”
The researchers looked at those methylation sites that were most strongly associated with mortality in greater detail.
Genes located around or near these sites are potential candidates for impacting lifespan or the risk of age-related disease.
For example, the gene PDZRN4 is a possible tumour suppressor, and ALPK2 is a gene implicated in cancer and heart health in animal models.
Other genes that stood out had previously been implicated in the development of cancer, osteoporosis, inflammation and metabolic syndrome.
“It would be intriguing to determine if genes like ALPK2 impact lifespan or health in animal models,” said Dr Adiv Johnson, the study’s last author and the head of Scientific Affairs and Education at Tally Health.
“Future studies are also needed to identify what other associations besides all-cause mortality can be captured with CheekAge.
“For example, other possible associations might include the incidence of various age-related diseases or the duration of ‘healthspan’, the period of healthy life free of age-related chronic disease and disability.”
