Why don't all our organs age at the same rate?

Did you think you were 43? In any case, that's the age they give you... but perhaps not that of your liver or your heart. Because all our organs do not age at the same speed. They wear out, in fact, to the rhythm of a biological clock that is specific to them, under the influence in particular of our environment and our lifestyles (smoking, alcohol, cholesterol, excess weight, etc.). Thus, a person's chronological age, which reflects the number of years since their birth, does not necessarily correspond to their biological age, the age their body actually has.

This is why some individuals are likely to suffer very early from diseases that normally appear with age, such as heart failure. This observation has led many teams to develop techniques to estimate the biological aging of individuals with the idea of ​​being able to predict these diseases, or even reverse their progression through anti-aging interventions. Using an artificial intelligence approach, a team from Stanford University in the United States has shown that it is possible to determine the age of our organs from simple blood tests. The results appeared in Nature Communications.

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To reach this conclusion, scientists looked at the proteins contained in the blood of 5,678 participants aged 20 to 90 years old. “Our organs actually release numerous proteins which are found in the plasma. By quantifying them, it is possible to determine their nature and therefore where they come from, which makes them good indicators of the activity of our organs,” explains Éric Gilson, director of the cancer research institute and the aging of Nice. Thanks to the analysis of nearly 5,000 circulating proteins, researchers identified that 900 of them were specific to an organ including the heart, lung, kidney, liver, muscle, pancreas, brain. , intestine, vascular system, immune system and fat. In the absence of known data, they considered that a protein came from a given organ if its expression was at least 4 times higher in this organ than in the others.

They then built an AI capable of estimating the biological age of each participant's organs to determine whether they were experiencing accelerated aging compared to the individuals' actual ages. To do this, they fed the algorithm with the protein levels measured in the participants' blood. By comparing the composition of these proteins in individuals of the same age, the AI ​​automatically detected those who had an aberrant protein level for a specific organ. The AI ​​then provided an “age gap”, that is to say a measure of the difference between the biological age of an organ and the civil age of the individual. “If for an organ of a given individual, this age difference was greater than the average for the group of individuals of the same age, then this meant that this organ was aging more quickly,” indicates Professor Gilson.

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First lesson: 18.4% of people aged 50 or over had at least one organ that aged significantly faster than the average while 1 in 60 people (i.e. 1.7%) presented accelerated aging in several organs. “What is interesting is that in addition, the researchers discovered that the age differences identified for all the organs studied, except the intestine, were significantly associated with the risk of death from all causes,” explains Miria Ricchetti, director of the Molecular Mechanisms of Pathological and Physiological Aging research group at the Pasteur Institute.

According to these estimates, premature aging of an organ would lead to an increase of 15 to 50% in the risk of mortality over the following fifteen years, depending on the organ affected. Participants whose hearts aged prematurely compared to average would be 2.5 times more likely to develop heart failure. Those with accelerated brain aging were at 1.8 times greater risk of cognitive decline, while having an “older” kidney than normal increased the risk of hypertension and diabetes.

Surprising results, which raise a question: will we be able, in the future, to go to the analysis laboratory to estimate the aging of our organs, predict the possible occurrence of an illness and make all medical decisions in advance? to prevent it from occurring? The hope is, to say the least, utopian at this stage of the research. “The study is very interesting because it involves the idea of ​​being able to use biomarkers as simple as circulating proteins to obtain a diagnostic signature of the state of organs and estimate the trajectories of aging,” underlines Professor Gilson. “The strength of this approach lies in the fact that it is very simple to obtain the biological material, namely blood,” adds Professor Ricchetti.

However, specialists agree, these “very preliminary” results are more of a proof of concept than a reliable method ready for routine use. Several verification steps will be necessary. And as the authors point out, the study will need to be replicated in larger cohorts and involve different ethnic groups, as genetic heritage and aging trajectories can vary greatly from one population to another.