A new way to reveal age-related disease risk

Determining a person’s “biological”, as distinct from chronological, age, may be as simple as a urine test, Chinese research has shown.

The idea that when it comes to age biology and chronology don’t always align is considered by many researchers to be debatable.

However, it is generally accepted that ageing rates between people born in the same year can and do vary by quite a wide margin, and there is a lot of interest in developing ways to both quantify and identify the mechanisms underpinning the difference.

The US National Health and Nutrition Survey (NHANES), for instance, is working on an algorithm based on 10 biomarkers to identify the risk factors that influence health and ageing.

In a trial study, the researchers from NHANES enrolled 9000 participants, aged between 30 and 75 years. During a two-decade follow-up, they found that the algorithm was better at predicting death than a simple chronological scale. However, they also observed that the majority of deaths occurred in participants at the older end of the cohort, leaving the question of whether it was useful for predicting outcomes for younger folk moot.

Another study, looking only at people aged between 26 and 38, and measuring 18 biomarkers, concluded that the risk of developing age-related chronic diseases was consistent with measurements for age-dependent decline. However, the researchers conceded that “measuring ageing remains controversial”.

One measure often suggested for assessing biological ageing is oxidation – the degree to which oxygen by-products called free radicals, produced during normal metabolism, can damage biomolecules.

In a new study, researchers led by Jian-Ping Cai of the MOH Key Laboratory of Geriatrics, in Beijing Hospital, China, focus on two biomarker that arises from the oxidation of RNA and DNA.

The biomarkers are called 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo) and 8-oxo-7, 8-dihydroguanosine (8-oxoGuo).

The first, which is a product of oxidisation in DNA, has long been known to increase in both mitochondrial and nuclear DNA with ageing.

Cai and colleagues wanted to know if the same applied to 8-oxoGuo, which arises from RNA oxidisation. They also wanted to know if increases in either progressed in a quantifiable manner – permitting a measure of ageing in the body that was independent of the number of years lived.

To test this, the scientists enrolled 1228 healthy Chinese volunteers, aged from two to 90. Urine samples were collected and their components measured using ultra-high-performance liquid chromatography with a triple quadrupole mass spectrometer.

The results showed that both substances did indeed increase in urine in line with the chronological age of the person. However, the RNA oxidiser, 8-oxoGuo, produced a much more accurate correlation than the DNA agent.

Interestingly, the team found that 8-oxoGuo levels in post-menopausal women were much higher than in men of the equivalent age. The result might reflect the decrease in oestrogen levels in older women, because oestrogen is known to be a powerful antioxidant.

The research, published in the journal Frontiers in Aging Neuroscience, clearly establishes a correlation between 8-oxoGuo levels and age, but Cai thinks future measurements may be more revealing.

“Urinary 8-oxoGsn may reflect the real condition of our bodies better than our chronological age, and may help us to predict the risk of age-related diseases,” he says.