We don’t all age at the same rate, but our tissues all age simultaneously. The cause is biological aging processes, but also a multitude of behavioral and lifestyle factors already known to accelerate aging, including stress, lack of sleep, poor diet, smoking and alcohol. While these environmental factors imprint their signature on our genome in the form of epigenetic marks, it becomes possible, with these new epigenetic clocks, to quantify molecular aging by characterizing the epigenome at prognostic genomic sites.
Several “epigenetic clocks” have been developedfocused on DNA methylation in blood cellsmaking sample collection tedious and stressful for the patient. This second-generation clock, called “CheekAge,” uses cell methylation data that is easier to collect.
“CheekAge” uses cells collected from the inside of the cheeks!
The study conducted by a New York team confirms CheekAge’s ability to accurately predict the risk of death from cheek cells – but also from epigenetic data from another tissue. On the other hand, the scientists confirm that the selection of specific methylation sites is particularly important for this prediction;
“which also reveals links between certain genes and specific processes of aging and mortality”adds one of the lead authors, Dr Maxim Shokhirev.
Thus the research reveals target genes like PDZRN4, a possible tumor suppressor, and ALPK2, already implicated in cancer and heart health, which could be candidates for reducing the risk of age-related disease.
CheekAge was nourished and perfected using methylation data from more than 200,000 sites, compared to an overall health and lifestyle score. Validation of its predictive capacity was carried out in 1,513 participants, women and men, born in 1921 and 1936 and followed throughout their lives by the Lothian Birth Cohorts at the University of Edinburgh. As part of this cohort, the methylome of participants was analyzed every 3 years, in blood cells and at approximately 450,000 DNA methylation sites. The analysis confirms that:
- CheekAge outperforms first generation clocks trained on blood cell datasets;
- for every single standard deviation increase in CheekAge, the hazard ratio for all-cause mortality is increased by 21%;
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in other words, CheekAge is strongly associated with mortality risk in older people;
- The CheekAge results, consistent with those of other epigenetic clocks based on blood cell data, suggest that there are indeed epigenetic mortality signals common to all tissues.
The simple collection of cells from the cheek, which is non-invasive, therefore constitutes a promising alternative for studying the biology of aging more simply and probably on larger samples.
