A few hundred of the thousands of proteins circulating in our blood turn out to be a fairly accurate forecaster of a person’s age, scientists reported Thursday — though one’s biological age, which doesn’t always match one’s number of years.
This “proteomic clock,” as the researchers call it, relies on measurements of levels of the proteins, which rise and fall over the years. While it’s a nifty discovery, for now it remains just that. Researchers need to first develop a much better understanding of these proteins; if they can, they said, it might be possible to one day look at their levels to gauge the success of drugs being tested in clinical trials, or even to develop a therapy from a cocktail of proteins that could act like a rejuvenation boost or improve health.
“Why are these proteins so tightly linked to aging?” said Tony Wyss-Coray, professor of neurology and neurological sciences at Stanford and the senior author of the paper, which was published Thursday in the journal Nature Medicine.
Researchers have known that the composition of our plasma — the liquid portion of the blood, absent the cells — changes as we get older. It’s why swapping blood from young mice into older rodents turns back the clock for some of their organ systems, and why doing the reverse can accelerate the aging process in young mice.
But there are a number of pathways involved in aging, and scientists have a limited understanding of them. The eventual hope is that researchers can manipulate mechanisms of aging to stave off diseases.
The new study was launched after Wyss-Coray and colleagues noticed that, when looking at the blood proteins of people with Alzheimer’s, the bigger differences weren’t between those people and healthy people their age, but between people of different ages.
For the study, the team looked at 2,925 proteins in blood from more than 4,200 adults, from 18 to 95 years old. To build their clock, they narrowed it down to 373 proteins, the levels of which together were predictive of age.
Based on their blood, some people appeared younger or older than their chronological age — that is, how many years they’ve been alive. In those cases, Wyss-Coray said, being biologically younger meant that people had better cognition and greater physical strength, meaning they functioned like younger people.
“It’s a whole new set of markers that we will be able to use to assess someone’s health,” said Dr. Eric Verdin, the chief executive of the Buck Institute for Research on Aging, who was not involved in the new research. Verdin likened the proteomic clock to the epigenetic clock, an age predictor based on chemical tags along a person’s DNA that influence gene expression.
Notably, Verdin said, proteins pulled from the blood come from all over the body, not just one tissue or organ system. That means a snapshot of the proteins can provide a glimpse of a person’s overall health that more specific tests might miss.
Verdin said going forward, he hoped the researchers would track people (and their plasma proteins) for a long period of time to determine, say, if the composition of proteins at age 40 is associated with early death or the development of heart disease or Alzheimer’s. If you have a heart attack at 60, he said, it’s likely the groundwork was laid years earlier; by dropping in on people’s protein levels, perhaps it might be possible to know who could benefit from some sort of intervention.
The researchers found that there was some regular fluctuation in the levels of proteins, but that there were three major shifts — what the scientists called “waves” or “crests” of changes — involving hundreds of proteins at three points in people’s lives: age 34, 60, and 78.
“Aging is not linear,” Wyss-Coray said. “It’s not that we steadily age as we get older. It seems that aging comes in waves.”
The study did not answer the question of whether the changes in these proteins’ levels were a reflection of aging or were themselves driving aging. But Wyss-Coray said the blood-swapping experiments between young and old mice suggests that the protein assortment does influence age-related changes more broadly.
If that’s the case, it might be possible to develop a therapy based on proteins for age-related conditions.
There was another key finding. The researchers found that levels of nearly 900 proteins that wavered with age differed between men and women. (The 373 proteins used to build the proteomic clock had changes independent of sex.)
Wyss-Coray said the finding validated efforts by U.S. health authorities to include more women in clinical trials and to account for sex as a biological variable.
And it wasn’t just sex hormones that were different, as might be expected, Wyss-Coray said.
“What’s more exciting is that there seem to be other unknown factors that contribute to these differences.”
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