Your real age is written in your blood
The study saw researchers examining blood samples and the levels of various proteins within them in order to accurately measure biological age, which is the true measure of how much someone has been affected by aging.
When compared with chronological age, such a test can measure how fast or slow a person is aging, and it could lead to tests that identify potential risks of developing specific age-related diseases earlier than is typically experienced. Additionally, having an accurate biomarker of aging also allows clinicians to verify the effectiveness of interventions that directly target the aging processes, which would obviously be very helpful as the field continues to develop them..
It also opens the door to slowing down or even reversing the changes to blood proteins that drive some aspects of aging. By calibrating blood levels of key proteins that control these aspects, it may be possible to rejuvenate tissue and keep people biologically younger and healthier, as has already been demonstrated to be possible in mouse studies by the same team of researchers and also by several other labs.
So, how is this possible? According to Dr. Tony Wyss-Coray, it all comes down to the composition of the proteins in the blood that regulate tissue regeneration. When we are younger, this cocktail of proteins supports healthy tissue repair and function, but, as we age, the balance of proteins shifts, and things stop working so well. Over time, the balance of these proteins changes and ultimately goes from being beneficial to actively driving aging, leading to poor tissue repair and ultimately organ failure.
Creating the proteomic clock
Dr. Wyss-Coray and his team have been researching these proteins for many years and have discovered evidence that it may be possible to rejuvenate the aging brain and other organs and tissues by manipulating these proteins. The researchers have been tracking age-related changes to blood protein levels in order to understand which of them are the primary targets for rejuvenation.
The team isolated plasma from over 4,200 healthy people aged between 18 to 95 years old and used around half of the participant data to build a “proteomic clock”, an aging clock that measures a person’s age based on the exact mixture and levels of blood proteins. They tested it on the other half of the participants whose data was not used to build the clock, finding that this proteomic clock could accurately ascertain their age.
The researchers examined a total of 3000 proteins for the proteomic clock but found that only 373 were needed to make accurate predictions. Even nine proteins were enough to predict someone’s age within a good margin.
The study spotlights the distinct changes that occur during aging, and the researchers recorded that people who were biologically younger according to their proteomic clocks were physically and cognitively better at tests than their biologically older counterparts.
The researchers found that some proteins present in blood do appear to change gradually over time; however, a number of other proteins increased or declined in a far more dramatic way. This means that the common idea that aging is a gradual decline is not entirely accurate; in fact, the evidence is that aging follows a somewhat more complex trajectory.
Perhaps most intriguing was the discovery that aging does not happen gradually as one might expect; it has periods of acceleration happening around ages 34, 60, and 78. For example, the researchers found that a protein secreted by neurons is present at a constant level throughout life up until around age 60, when it rises dramatically; the reason for this huge increase is as yet unknown, but it does highlight the somewhat erratic path that aging takes.
Aging is a predominant risk factor for several chronic diseases that limit healthspan. 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. We measured 2,925 plasma proteins from 4,263 young adults to nonagenarians (18–95 years old) and developed a new bioinformatics approach that uncovered marked non-linear alterations in the human plasma proteome with age. Waves of changes in the proteome in the fourth, seventh and eighth decades of life reflected distinct biological pathways and revealed differential associations with the genome and proteome of age-related diseases and phenotypic traits. This new approach to the study of aging led to the identification of unexpected signatures and pathways that might offer potential targets for age-related diseases.
This builds on the research that the Wyss-Coray Lab, the Conboy Lab, and others have conducted into blood factors and their influence over aging. Taken together, these new findings suggest that the proteomic clock may be a useful aging biomarker and show that blood factors play an important role in aging. Indeed, altered intercellular communication, the chemical signals secreted by cells into the bloodstream – the ultimate communication superhighway linking everything in the body – is one of the hallmarks of aging, and this research further supports that.
The next step for the team will be to continue delving into these findings in order to discover the origin of changes to the key blood proteins that regulate aging. What they discover is likely to have ramifications for health and might even spur the development of methods to rewind the proteomic clock to make us biologically younger in certain ways. This has already been demonstrated as being possible in animals; the next step is translating it to humans.
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 Lehallier, B., Gate, D., Schaum, N., Nanasi, T., Lee, S. E., Yousef, H., … & Sathyan, S. (2019). Undulating changes in human plasma proteome profiles across the lifespan. Nature Medicine, 25(12), 1843-1850.