Aging clocks misread biological age in mixed-ancestry groups

Aging clocks are tools that estimate biological age from methylation patterns (chemical tags on DNA that regulate which genes are active). Biological age can diverge from chronological age and is linked to the risk of diseases such as Alzheimer’s. These clocks are already used in research and are beginning to enter clinical settings.

But the study, published in eLife, shows that these clocks are considerably less accurate in people of African or Latin American descent. The researchers analysed data from more than three thousand individuals across multiple datasets, including African Americans, Hispanics, and people of European ancestry. In groups with a substantial African genetic component, none of the tested clocks reliably detected accelerated aging in Alzheimer’s patients compared to controls.

Why do the clocks fail?

The researchers looked for the cause. They found that the methylation patterns at the specific DNA sites used by the clocks differ systematically between populations with African and European genetic backgrounds. This is partly because genetic variants (known as meQTLs) that influence methylation at those sites are more common in people of African ancestry.

Consequences for practice

The clocks were largely developed and validated in populations of European ancestry. Applying them to broader populations may produce inaccurate risk estimates. People with mixed ancestry could be incorrectly classified as biologically younger or older. The researchers call for the clocks to be retrained on genetically diverse datasets. Until that happens, results in diverse populations should be interpreted with caution.

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