January 7, 2020

Blood protein signatures change across lifespan

At a Glance

  • Levels of around 400 proteins in the blood accurately reflected people’s age and relative health.
  • More research is needed to understand if such a protein signature could help identify people at greater risk of age-related diseases.
Portrait of grandmother, mother, and daughter The study found three large peaks of change in blood proteins across the human lifespan. fizkes / iStock / Getty Images Plus

The bloodstream touches all the tissues of the body. It carries nutrients to tissues and takes waste products away. Tissues also release proteins into the bloodstream that can communicate with other parts of the body, help mount an immune response to disease, and much more.

Because of this constant flow of proteins through the body, some blood tests measure specific proteins to help diagnose diseases. Examples include diabetes, heart disease, and kidney and liver problems. Scientists have been curious about whether blood proteins could be used to more broadly assess people’s health and wellness.

To explore this idea further, researchers led by Drs. Benoit Lehallier and Tony Wyss-Coray from Stanford University collected blood plasma samples from more than 4,000 volunteers between the ages of 18 and 95. They compared the levels of nearly 3,000 proteins in blood between people of different ages as well as between men and women within those age groups. The work was funded in part by NIH’s National Institute on Aging (NIA). Results were published on December 5, 2019, in Nature Medicine.

Overall, about two-thirds of the proteins found to change with age differed between men and women. This supports the idea that men and women age differently—and highlights the need to include both sexes in clinical studies for a wide range of diseases.

The researchers identified a subset of 373 proteins that could accurately predict people’s age within a range of a few years in both men and women. Participants who were predicted by their protein signature to be younger than they actually were performed better than their peers on cognitive and physical tests.

Unexpectedly, deeper analyses showed that most protein changes seen with aging did not occur in a linear fashion. Instead, they occurred in waves, with three large peaks of change around the ages of 34, 60, and 78. These waves largely consisted of changes in different proteins and were associated with different biological functions.

Some of the proteins found in these peaks had previously been associated with the development of age-related diseases. For example, proteins associated with cardiovascular disease and Alzheimer’s disease were found in the peaks at 60 and 78 years of age.

“We’ve known for a long time that measuring certain proteins in the blood can give you information about a person’s health status—lipoproteins for cardiovascular health, for example,” says Wyss-Coray. “But it hasn’t been appreciated that so many different proteins’ levels—roughly a third of all the ones we looked at—change markedly with advancing age.”

More research is needed to understand what protein signatures might help identify people at greater risk of age-related diseases. Such signatures could have potential for helping diagnose diseases like Alzheimer’s disease, for which no blood tests currently exist. The findings may also help identify potential targets for preventing and treating age-related diseases.

—by Sharon Reynolds

Related Links

References: Undulating changes in human plasma proteome profiles across the lifespan. Lehallier B, Gate D, Schaum N, Nanasi T, Lee SE, Yousef H, Moran Losada P, Berdnik D, Keller A, Verghese J, Sathyan S, Franceschi C, Milman S, Barzilai N, Wyss-Coray T. Nat Med. 2019 Dec;25(12):1843-1850. doi: 10.1038/s41591-019-0673-2. Epub 2019 Dec 5. PMID: 31806903.

Funding: NIH’s National Institute on Aging (NIA); Hungarian Brain Research Program; Fulbright Foreign Student Program; Cure Alzheimer’s Fund; Nan Fung Life Sciences; NOMIS Foundation; Stanford Brain Rejuvenation Project; Paul F. Glenn Center for Aging Research; American Federation for Aging Research; Glenn Center for the Biology of Human Aging.