From the NIH Director’s Blog by Dr. Francis Collins
How can you tell how old someone is? Of course, you could scan their driver’s license or look for signs of facial wrinkles and gray hair. But, as researchers just found in a new study, you also could get pretty close to the answer by doing a blood test.
That may seem surprising. But in a recent study in Nature Medicine, an NIH-funded research team was able to gauge a person’s age quite reliably by analyzing a blood sample for levels of a few hundred proteins. The results offer important new insights into what happens as we age. For example, the team suggests that the biological aging process isn’t steady and appears to accelerate periodically — with the greatest bursts coming, on average, around ages 34, 60, and 78.
These findings indicate that it may be possible one day to devise a blood test to identify individuals who are aging faster biologically than others. Such folks might be at risk earlier in life for cardiovascular problems, Alzheimer’s disease, osteoarthritis, and other age-related health issues.
What’s more, this work raises hope for interventions that may slow down the “proteomic clock” and perhaps help to keep people biologically younger than their chronological age. Such a scenario might sound like pure fantasy, but this same group of researchers showed a few years ago that it’s indeed possible to rejuvenate an older mouse by infusing blood from a much younger mouse.
Those and other earlier findings from the lab of Tony Wyss-Coray, Stanford School of Medicine, Palo Alto, CA, raised the tantalizing possibility that certain substances in young blood can revitalize the aging brain and other parts of the body. In search of additional clues in the new study, the Wyss-Coray team tracked how the protein composition of blood changes as people age.
To find those clues, they isolated plasma from more than 4,200 healthy individuals between ages 18 and 95. The researchers then used data from more than half of the participants to assemble a “proteomic clock” of aging. Within certain limits, the clock could accurately predict the chronological age of the study’s remaining 1,446 participants. The best predictions relied on just 373 of the clock’s almost 3,000 proteins.
As further validation, the clock also reliably predicted the correct chronological age of four groups of people not in the study. Interestingly, it was possible to make a decent age prediction based on just nine of the clock’s most informative proteins.
The findings show that telltale proteomic changes arise with age, and they likely have important and as-yet unknown health implications. After all, those proteins found circulating in the bloodstream come not just from blood cells but also from cells throughout the body. Intriguingly, the researchers report that people who appeared biologically younger than their actual chronological age based on their blood proteins also performed better on cognitive and physical tests.
Most of us view aging as a gradual, linear process. However, the protein evidence suggests that, biologically, aging follows a more complex pattern. Some proteins did gradually tick up or down over time in an almost linear fashion. But the levels of many other proteins rose or fell more markedly over time. For instance, one neural protein in the blood stayed constant until around age 60, when its levels spiked. Why that is so remains to be determined.
As noted, the researchers found evidence that the aging process includes a series of three bursts. Wyss-Coray said he found it especially interesting that the first burst happens in early mid-life, around age 34, well before common signs of aging and its associated health problems would manifest.
It’s also well known that men and women age differently, and this study adds to that evidence. About two-thirds of the proteins that changed with age also differed between the sexes. However, because the effect of aging on the most important proteins of the clock is much stronger than the differences in gender, the proteomic clock still could accurately predict the ages in all people.
Overall, the findings show that protein substances in blood can serve as a useful measure of a person’s chronological and biological age and — together with Wyss-Coray’s earlier studies— that substances in blood may play an active role in the aging process. Wyss-Coray reports that his team continues to dig deeper into its data, hoping to learn more about the origins of particular proteins in the bloodstream, what they mean for our health, and how to potentially turn back the proteomic clock.
Reference:
[1 ] Lehallier B, et al. Undulating changes in human plasma proteome profiles across the lifespan. Nat Med. 2019 Dec;25(12):1843-1850.
NIH Support: National Institute on Aging
I'm an enthusiast with a deep understanding of the fascinating field of proteomics and its implications in understanding the aging process. My expertise is grounded in the latest research, such as the study highlighted in the NIH Director's Blog by Dr. Francis Collins. This study, published in Nature Medicine and supported by the National Institute on Aging, unveils groundbreaking insights into determining a person's age through a blood test.
The research, led by a team funded by the NIH, particularly Tony Wyss-Coray from Stanford School of Medicine, delves into the proteomic changes that occur in the bloodstream across a person's lifespan. By analyzing blood samples from over 4,200 healthy individuals aged 18 to 95, the researchers created a "proteomic clock" of aging. This clock relies on the levels of a few hundred proteins, and remarkably, accurate predictions of chronological age were possible with just 373 of these proteins.
The study revealed that the aging process isn't a steady, linear progression but rather occurs in periodic bursts, with significant changes around ages 34, 60, and 78. This challenges the conventional view of aging as a gradual process. The proteomic clock not only accurately predicted age but also demonstrated differences between men and women, with two-thirds of the proteins changing with age differing between the sexes.
What makes this research even more intriguing is its potential applications. The study suggests the development of a blood test to identify individuals aging faster biologically, putting them at higher risk for age-related health issues like cardiovascular problems and Alzheimer's disease. Furthermore, the findings open doors to interventions that could potentially slow down the proteomic clock, offering hope for keeping individuals biologically younger than their chronological age.
The team's earlier work, which involved rejuvenating older mice by infusing them with blood from younger mice, supports the notion that substances in young blood might have revitalizing effects on the aging body and brain. The study also found that individuals who appeared biologically younger based on blood proteins performed better on cognitive and physical tests.
In summary, this research contributes valuable knowledge to our understanding of the aging process, highlighting the role of blood proteins as a measure of both chronological and biological age. As the team continues to delve into their data, we can anticipate learning more about the origins and implications of specific proteins in the bloodstream and the potential for manipulating the proteomic clock.
Reference: Lehallier B, et al. Undulating changes in human plasma proteome profiles across the lifespan. Nat Med. 2019 Dec;25(12):1843-1850. NIH Support: National Institute on Aging [1].
