Blood proteins and molecular changes that occur in our blood could be used to assess our health and wellness and more specifically identify people at greater risk of age-related diseases, according to a new study by researchers at Stanford University and funded in part by NIH’s National Institute on Aging (NIA).
Researchers led by Drs. Benoit Lehallier, PhD and Tony Wyss-Coray, PhD, have discovered three large peaks of change in blood proteins across the human lifespan, and that the levels of around 400 proteins in the blood accurately reflected people’s age and relative health. They published their results December 5 in Nature Medicine. Wyss-Coray, a professor in the Department of Neurology and Neurological Sciences at Stanford is the senior author. The lead author is Stanford neurology instructor Lehallier.
Because the bloodstream touches all the tissues of the body carrying nutrients to tissues and taking waste products away, some blood tests measure specific proteins that assist in diagnosing diseases like diabetes, heart disease and kidney and liver problems.
In a study of blood samples from more than 4,000 volunteers ages 18 to 95, researchers compared the levels of nearly 3,000 proteins in blood between people of different ages as well as between men and women to find out whether blood proteins could be used to more broadly assess people’s health and wellness.
“Overall, about two-thirds of the proteins found to change with age differed between men and women,” the National Institutes of Health (NIH) reported. “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.”
Stanford researchers identified a subset of 373 proteins that could accurately predict one’s age within a range of a few years in both men and women, the NIH reported.
“Aging is a predominant risk factor for several chronic diseases that limit healthspan,” scientists reported in their study. “Mechanisms of aging are thus increasingly recognized as potential therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues, which supports a hypothesis that age-related molecular changes in blood could provide new insights into age-related disease biology.”
In measuring some 2,925 plasma proteins from 4,263 young adults to nonagenarians, scientists led by Lehallier and Wyss-Coray developed a new bioinformatics approach that “uncovered marked non-linear alterations in the human plasma proteome with age.” The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue or organism at a certain time.
In 2014, researchers headed by Drs. Akhilesh Pandey at Johns Hopkins University and Harsha Gowda at the Institute of Bioinformatics in Bangalore, India, and funded in part by the NIH, the National Cancer Institute (NCI) and the National Heart, Lung and Blood Institute (NHLBI), used an advanced form of mass spectrometry to sequence proteins and create a draft map of the human proteome. In 2003, the Human Genome Project created a draft map of all of the genes in the human body—the human genome. Since then, genomics has since driven many advances in medical science.
According to the NIH, though researchers have identified more than 20,000 protein-coding genes, scientific understanding of the proteome has lagged behind that of the genome, partly because of the proteome’s complexities. “The relationship between genes and proteins isn’t a simple matter of one gene coding for one protein,” the NIH reports. “Stretches of DNA can be read and translated into proteins in different ways. Proteins are also more difficult to sequence than genes.”
In the Stanford study, people whose ages were guessed to be younger by their protein signature actually 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,” the NIH reported. “Instead, they occurred in waves, with three large peaks of change around the ages of 34, 60 and 78.”
These “waves of changes” in the proteome in the fourth, seventh and eighth decades of life largely consisted of changes in different proteins and were associated with different biological functions. This new bioinformatics approach to the study of aging led to the identification of unexpected signatures and pathways that might offer potential targets for age-related diseases, the scientists reported.
Some of the proteins found in these peaks have already been associated with the development of age-related diseases. In fact, proteins associated with cardiovascular disease and Alzheimer’s disease were found in the peaks at 60 and 78 years of age.
In essence, scientists found they could determine age by a kind of physiological clock: the levels of 373 proteins circulating in your blood. And this clock could help determine important things about your health.
“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,” said Wyss-Coray, PhD, also the D. H. Chen Professor II and co-director of the Stanford Alzheimer’s Disease Research Center. “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.”
Human tissues also release proteins into the bloodstream that can communicate with other parts of the body, helping to mount an immune response to disease, and much more. Wyss-Coray added that changes in the levels of proteins that migrate from the body’s tissues into circulating blood not only characterize, but quite possibly cause, the phenomenon of aging.
“More research is needed to understand what protein signatures might help identify people at greater risk of age-related diseases,” the NIH reported. “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.”