Blood samples may be necessary for accurate biological age testing

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Researchers warn that saliva and cheek swabs may overestimate biological age by decades, raising concerns over commercial testing accuracy.

Estimating biological age – a measure of how well an individual’s body is functioning compared with their chronological age – has become an increasingly popular method of assessing health and longevity; however, a new study led by researchers from Penn State University suggests that the accuracy of such tests depends heavily on the type of tissue sample used. Published in Aging Cell, the findings indicate that while blood samples yield reliable results, biological age estimates derived from oral tissue – such as saliva or cheek swabs – can be significantly inflated [1].

Longevity.Technology: The growing popularity of biological age testing reflects a wider interest in understanding and improving longevity – however, accuracy should not be sacrificed for the sake of convenience. While saliva-based tests are more accessible and easier to collect, the evidence presented in this study suggests that they may produce misleading results. Given the potential impact of biological age assessments on healthcare and lifestyle choices, ensuring that testing methods are both scientifically valid and appropriately matched to the epigenetic clocks in use is essential. Without this rigor, individuals may be misled about their biological health and take actions based on unreliable information.

Epigenetic clocks and the importance of tissue type

Epigenetic clocks are tools developed by researchers to estimate biological age by analyzing DNA methylation – a process that influences gene activity without altering the DNA sequence itself. These clocks are constructed by collecting tissue samples from a large number of individuals and identifying patterns in DNA methylation that correlate with chronological age. However, as the Penn State study demonstrates, the tissue type used in testing plays a crucial role in the accuracy of these estimates.

Blood samples outperform oral tissue in accuracy

The study evaluated five types of tissue samples – three blood-based and two oral-based – against seven widely used epigenetic clocks. Researchers examined 284 tissue samples from 83 individuals between the ages of nine and 70 and found that in six of the seven clocks tested, oral tissues produced substantially higher biological age estimates than blood samples [1].

“We tested three types of blood samples and two types of oral tissues – saliva and cheek swabs,” said Abner Apsley, doctoral candidate in the Penn State Molecular, Cellular and Integrative Biosciences Graduate Program. “For almost every epigenetic clock, the oral tissue led to significantly higher estimates of the subject’s biological age. In some cases, the estimates were 30 years higher; that is extremely inaccurate. It is very clear that the tissue used to measure someone’s biological age must match the tissue used when the clock was created. Otherwise, estimates of biological age will not be valid [2].”

Blood samples, on the other hand, produced consistent and reliable estimates across different epigenetic clocks. The one exception to the trend was an epigenetic clock developed using both blood and cheek swabs; in that case, the age estimates were found to be more accurate across both tissue types [1].

Implications for commercial biological age testing

The findings raise concerns about the accuracy of commercial biological age tests, many of which rely on saliva samples provided by customers. Some companies offer testing services in which individuals submit a saliva sample by mail, which is then analyzed to estimate biological age using existing epigenetic clocks. However, since most clocks were developed using blood samples, the Penn State study suggests that results from saliva-based tests may be unreliable.

“Most of the popular clocks were created using blood samples,” Apsley noted. “So, these results represent an important lesson for this burgeoning field. If companies or physicians want to use saliva or cheek swabs to measure biological age, then researchers need to develop epigenetic clocks using those tissues. Currently, blood is needed to accurately estimate biological age in most circumstances [2].”

Potential future applications of biological age measurements

Despite current limitations in accuracy, biological age estimates may become a valuable tool in medical decision-making. The researchers suggest that biological age could help identify patients who might benefit from early interventions to delay the onset of age-related diseases or determine which individuals are well-suited for certain medical procedures.

“Aging is the main driver for a host of common diseases including dementia, heart disease and cancer,” Idan Shalev, associate professor of biobehavioral health at Penn State, said. “Biological age measurement is not a diagnosis of a health problem, but it can be used to identify a person’s risk for age-related conditions [2].”

Beyond healthcare applications, epigenetic clocks have also been used in forensic science, offering a method to estimate the approximate age of suspects based on biological samples collected at crime scenes.

“Researchers are still discovering how to apply biological age,” said Shalev. “Our research focuses on medical applications, but epigenetic clocks have also been used with blood samples from crime scenes to help forensic scientists identify the approximate age of criminal suspects. Who knows where this field will lead us next? [2]”

With continued research, biological age testing may eventually become an integral part of healthcare – offering insights into disease risk, treatment suitability and longevity; for now, however, blood samples remain the gold standard for obtaining accurate estimates of biological age.