One organ in a person’s body can age faster than the rest — with implications for health and mortality.
Max Kozlov
Scientists studied more than 5,000 people to understand variation in the ageing of individual body organs.Credit: Christopher Furlong/Getty
As people age, their cells undergo a raft of biochemical changes that lead to organ damage and, eventually, death. But a new study1 that tracks proteins suggests that these changes aren’t uniform: an individual’s organs can age at different rates, and a given organ can age at a faster rate in one person than in another with the same chronological age.
The authors studied 11 major organs and report that all of them can be subject to ‘accelerated’ ageing, as defined by the levels of certain proteins in the blood. Around one-fifth of the more than 5,600 people who participated in the study met the authors’ criteria for accelerated ageing for at least one organ. Such hyper-aged organs are linked to a higher prevalence of disease, and having one organ of unusually advanced age is linked to a higher risk of premature death, the study found.
Tests for proteins related to organ age could help researchers to develop treatments for age-related health problems and could also guide personalized treatment plans, says Hamilton Oh, a computational biologist at Stanford University in California and a study co-author. Physicians already monitor patients’ levels of some proteins, and the authors’ test “would be expanding their toolkit”, he says.
The paper was published today in Nature.
Ageing by numbers
Previous research2 has identified several hallmarks of ageing at the cellular level, such as the accumulation of DNA mutations and changes in the epigenome, the collection of chemical tags on a person’s DNA. Over the past decade, researchers have developed algorithms that harness these indicators to estimate a person’s ‘biological age’, which can be higher or lower than their chronological age3.
First hint that body’s ‘biological age’ can be reversed
Another hallmark of ageing is a shift in the proteins that the body produces. To explore how organs age, Oh and his colleagues first analysed nearly 5,000 proteins in blood samples from 1,398 healthy adults. They identified about 850 proteins that originated mainly from a single organ and trained a machine-learning algorithm to predict a person’s age on the basis of the levels of these proteins. They validated their model using blood samples from more than 4,000 other people.
The results showed that an organ’s biological age is linked to disease risk. For example, roughly 2% of participants had accelerated heart ageing — that is, their levels of blood proteins relating to heart ageing differed substantially from those of other people of the same age. Having a prematurely old heart was linked to a 250% increased risk of heart failure, the authors found.
Marking time
Some researchers have used epigenetic markers to show that the pace of organ ageing varies between individuals4. But it’s not clear how epigenetic changes are linked to ageing, says Matt Kaeberlein, a specialist in the biology of ageing and chief executive of Optispan, a biotechnology company in Seattle, Washington. Proteins are “much closer to the downstream mechanisms that might be driving ageing”, he says. Protein biomarkers might help researchers to identify targets for anti-ageing drugs, he adds.
Combining various hallmarks of ageing could lead to more robust tests of organ age than protein tests alone, says Sara Hägg, an epidemiologist at the Karolinska Institute in Stockholm who specializes in biological ageing. She praises the “impressive” amount of data the researchers analysed, but cautions that it’s not clear whether the proteins are driving the ageing process or are by-products of it. It’s also unclear whether the team’s algorithm predicts disease risk or simply reflects protein changes caused by diseases, she says.
Kaeberlein says that determining causality is important, but time-consuming. In the meantime, with further research, these protein biomarkers might “help people by directing them to change their lifestyle or take some supplement”, he says. “That’s powerful regardless of causality.” Several tests that use biomarkers to assess ageing are already on the market, but Kaeberlein cautions against relying on these. The idea of having a non-invasive way to predict organ health from one sample is exciting, but “we don’t have a good understanding if these clocks are actionable or precise yet”, he adds.
doi: https://doi.org/10.1038/d41586-023-03821-w
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