A “clock” based on about 200 proteins in the blood can predict a person’s risk of developing 18 chronic diseases, including Heart disease, cancer, diabetes and Alzheimer's disease.

The clock's accuracy suggests the possibility of developing a single test that could describe a person's risk of many chronic diseases, says the project's lead scientist Austin Argentieri, a population health researcher at Massachusetts General Hospital in Boston. “Ultimately, the desire to live longer will come down to preventing chronic disease,” he says. The study was conducted on August 8thNature Medicinepublished 1.

Aged well

A person's chronological age is crucial in determining their risk for many age-related diseases. But chronological age is not a perfect predictor of disease. For example, some 60-year-olds are weak and suffer from heart disease, while others are perfectly healthy.

Argentieri and his colleagues tried to build a “clock” that would accurately reflect a person’s disease status. To do this, they used data from 45,441 randomly selected people UK Biobank, a repository for biomedical samples. This sample size is approximately 30 times larger than that used in a previous protein clock study, making it more statistically powerful.

The team found that levels of 204 proteins accurately predict chronological age. What's notable is that the authors created a second clock that used only the 20 most informative proteins, and it predicted age almost as well as the 204 protein clock. The 20 proteins included elastin and collagen, which form the support structure between cells, as well as proteins involved in immune response and hormone regulation.

The clock also accurately predicted chronological age in two other groups of people: nearly 4,000 contributors to a biobank in China and nearly 2,000 contributors to a biobank in Finland. Previous protein-based clocks looked at data from more homogeneous populations, the researchers say.

In general, age measured with the protein clock was similar to chronological age. But in some people there was a discrepancy between the two - indicating that protein levels change as disease develops. People whose protein clock age was higher than their chronological age were more likely to develop 18 chronic diseases, including diabetes, neurodegenerative diseases, cancer, as well as diseases of the heart, liver, kidneys and lungs. Protein clock age was also linked to physical frailty, slow reaction time and premature death.

Other people's proteins age slower than average. Whether this is due to environmental factors, genetics, or a combination thereof is unclear. Of the 10% of participants in the study who were "the slowest ageers," Argentieri says, "less than 1% developed dementia or Alzheimer's."

Turn back the clock?

The study's strengths include its large data set and its successful replication in different populations, says molecular epidemiologist Sara Hägg at the Karolinska Institute in Stockholm. “It’s a very robust study,” she says.

Argentieri and his colleagues want to add more geographic and genetic diversity to their training data. The limiting factor, says Argentieri, is the lack of protein data in biobanks with diverse populations. The authors are also exploring using their protein clock to test whether new medical treatments avert age-related ailments "without having to wait a decade or two to see if someone develops a chronic disease," Argentieri says.

Finally, they look for environmental and behavioral factors that influence how quickly proteins age in the body. “OK, you can tell me about my future risk for 18 different diseases,” Argentieri says. “But is there anything I can do to change this course?”