Not only age makes the human brain age

Some scientists have delved into a process that makes the human brain age regardless of the influence exerted by age.

Led by Argentine biologist David Furman, director of the 1000 Immunomas Project at Stanford University in the United States, and professor at the Buck Institute for Research on Aging, researchers from the United States have verified that, regardless of age, chronic levels High levels of certain inflammatory immune proteins circulating in the blood accelerate the aging process of the brain, but not in a homogeneous way. The finding could favor the development of tests that measure the rate of aging or have preventive and therapeutic repercussions for the elderly.

The study has been carried out in collaboration with colleagues from the University of California at San Francisco (UCSF) in the United States.

Furman, Nikola Markov of the Buck Institute, and their colleagues have found that while both age and chronic inflammation age the brain, each does so differently.

While the effect of age correlates with changes in the system that translates neuronal signals into movement, the blood concentration of inflammatory immune proteins affects processes such as attention, memory, emotion, and self-awareness.

For the study authors, “the identification of these immunological biomarkers related to brain aging could make them therapeutic targets for the prevention of age-related cognitive decline.”

In dialogue with the CyTA-Leloir Agency, Furman explained that the relationship between the immune system and aging began to become evident at the beginning of the year 2000, when Claudio Franceschi, then a researcher at the University of Bologna, Italy, summarized in an academic article that Elderly people have increased levels of circulating inflammatory proteins in the blood.

“From that moment on, a lot of research began to be done to understand how the inflammatory factors produced by cells of the immune system aged tissues, as well as others that become inflammatory under different conditions: endothelial cells, fibroblasts , mesenchymal cells or astrocytes”, assured the CONICET associate researcher (currently on leave) and current director of the “1000 Immunomas Project” at Stanford University, United States, which was launched in 2007 with the aim of answer that question. The initiative had some 70 million dollars contributed by the US National Institutes of Health (NIH), whose support has just been renewed for five more years, Furman reported.

Argentine biologist David Furman (left) led the study. (Photo: D. Furman)

The new study was born out of a collaboration with Joel Kreimer, a clinical psychologist and researcher at UCSF. It involved a cohort of 554 people in whom inflammatory factors were measured in the blood and, in addition, their brains were monitored through magnetic resonance imaging. Using artificial intelligence, the scientists also developed a biological clock that they named CyClo, which made it possible to accurately determine the age of the participants based on the presence of certain immune proteins (placental growth factor, vascular endothelial growth factor, or VEGF). , and 22 more).

“There are inflammatory processes that contribute to this biological clock and have an impact on the blood-brain barrier, causing a ‘leaky brain’ (defective or “permeable” brain): the theory is that there are cells that, when infiltrating different brain regions, produce inflammatory factors in situ, which generates a dysfunction at the neuronal level that increases the risk of cognitive deterioration”, described Furman, who explained that they analyzed the data obtained based on seven networks or functional pathways related to different activities of the brain (not with anatomical regions).

“Chronological aging, age, has a greater influence on certain motor areas; gender or sex, on areas of execution (women would have better problem-solving capacities); and immune proteins, on fine motor skills and the possibility of thinking about oneself, ”she assured.

question of inflammation

“In 2019 we published a study in Nature Medicine where we analyzed the difference between acute inflammation, such as that which occurs in asthma, and chronic systemic inflammation,” said the also head of the Buck Institute’s Center for Artificial Intelligence and Data Science on Aging. And he added that chronic inflammation can be due to age, but also to inflammation in the tissues, and that there are cases in which it is chronic but not systemic (as occurs with the lungs in tuberculosis).

“We are redefining the entire field of inflammation study so that we can understand what all the subtypes are,” Furman said, noting that they are now engaged in longitudinal study of the 554 patients to measure the different proteins continuously over time. and, thus, to be able to determine aging trajectories at the individual level.

“This is very interesting because it can give us an idea of ​​the aging rates; there are people who age faster than others, but the truth is that one can start with a given rate and have it accelerate or not due to lifestyle or ‘exposome,’” said Furman. And he mentioned some of the many environmental factors that trigger inflammatory processes in older people: hormone disruptors like ingredients in plastics; pesticides, which destroy the microbiota, whose diversity also deteriorates with a certain type of diet; air pollution; disruption of the circadian clock due to night work or constant change of time zone; high levels of social stress that do not allow cortisol to be able to contain the reaction, among others.

Although at present it is not yet possible to know the level of inflammatory proteins in a person through a simple blood sample, Furman’s bet is to achieve it. “This is what the so-called precision medicine tends to do, which is not only related to genetics, but can also be applied to this topic. We are talking about well-being, about prevention, ”he pointed out. And he estimated that with greater investment and more extensive studies, an accurate and accessible test could be available in about three or four years.

The study is titled “Age-related brain atrophy is not a homogenous process: Different functional brain networks associate differentially with aging and blood factors”. And it has been published in the academic journal Proceedings of the National Academy of Sciences (PNAS). (Source: CyTA-Leloir Agency)