Studies conducted in various countries indicate that approximately 60% of people over the age of 65 currently live with two or more chronic conditions simultaneously. With the aim of reversing this trend and promoting healthy aging, European researchers have created a new personalized indicator that provides a detailed snapshot of a patient's metabolism by analyzing, with high precision, the chemicals the body produces to function.
Presented during FAPESP Week Netherlands by Joris Deelen of Leiden University Medical Center (LUMC), the indicator serves as a general marker of health in middle age, enabling the early identification of those on a healthy aging trajectory and those at higher risk of functional decline. The initiative is particularly relevant in Europe given the wide variation in healthy life expectancy, Deelen noted.
"The length of time spent in good health after age 65 varies dramatically across Europe: in Romania, it's about four years, while in the Netherlands, it's ten years," he compared. "That disparity stems primarily from socioeconomic status, educational level, lifestyle, and genetic factors."
Since it is not possible to directly measure biological aging, the team – which also included scientists from the Max Planck Institute for Biology of Aging in Cologne, Germany – decided to look for answers in the blood of 44,000 volunteers who were followed over several years in 12 studies conducted across Europe. Through detailed blood tests, they measured more than 200 substances, including fat and sugar levels and markers of inflammation.
Over the course of the research, 5,500 deaths were recorded among the volunteers followed. By analyzing these individuals' blood, the researchers identified which substances serve as a biological warning sign for an increased risk of mortality.
The group then established a direct collaboration with Brazil to optimize the indicator. "We had an exchange student from São Paulo [Gabriela Natalle Lopes, a student at the Albert Einstein Israelite Faculty] who came to Leiden and worked with us to update the score, making it personalized and better suited for clinical interventions," Deelen reported.
The tool was updated in three stages. First, the scientists adjusted the mathematical calculation using data from the Dutch population, enabling the test to generate a unique, personalized result for each patient. Next, to make it easier to use in everyday clinical practice, they simplified the test: instead of hundreds of items, the tool now focuses on just ten blood markers that doctors are already accustomed to evaluating. Finally, the team reversed the logic of the score so that anyone can easily understand it. "In the original scoring, a high number was bad; we decided to change it so that a higher score indicates better health," Deelen explained.
The new version proved to be even more effective in predicting cardiometabolic diseases (such as diabetes, heart attack, and stroke). According to the researcher, a one-point increase on this new scale corresponds to an average delay of 14 years in the onset of the first cardiometabolic disease.
Practical interventions
Because it reflects the body's overall functional status, the score correlates with various parameters of healthy aging, such as cognitive function, lung capacity, and handgrip strength (which reflects overall muscle function).
To test whether the indicator could be modified through practical actions, the scientists had groups of volunteers undergo lifestyle changes and strength training programs. The results showed a striking pattern: the interventions led to significant improvements specifically in individuals considered less healthy (those with an initial score below average). In this higher-risk group, behavioral changes and exercise significantly reduced fasting insulin levels and triglycerides (fats circulating in the blood), in addition to improving body composition.
"When we analyzed the change in the group's score, we didn't see a significant change; however, when we divided the individuals by their initial score, we saw that the lifestyle intervention was specifically effective for those with a score below zero – that is, the people who were less healthy at the beginning," Deelen explained. "That indicates that the score is an excellent indicator for identifying who really needs intervention and for monitoring the health gains provided by exercise."
The analyses conducted by the group revealed that the metabolic score is determined 40% by heredity (genetics) and 60% by lifestyle and environmental factors. Among the behaviors analyzed, smoking emerged as the negative factor with the greatest impact on the metabolic score. On the other hand, increased regular physical activity reduces risk and improves the score.
The researcher also emphasized that events occurring in the early stages of human development leave permanent consequences: "Even malnutrition in childhood raises the metabolic score of those individuals later in adulthood," the professor noted.
Muscle-brain communication
The premise put forward by the Dutch study – that physical activity and overall metabolic health determine longevity and protection against functional decline – is given a detailed biological explanation in research conducted at the Federal University of São Carlos (UFSCar) in Brazil. Research led by Professor Tiago da Silva Alexandre reveals that musculoskeletal aging and dementia are closely linked by continuous molecular communication ("crosstalk") between four vital tissues: muscle, bone, fat, and the brain.
This biochemical "dialogue" between these structures occurs through the release of myokines – signaling and protective substances secreted by muscle tissue during movement. However, as we age, there may be an increase in fat infiltration within muscle fibers. This change compromises not only contractile capacity and metabolic rate but also the functional integrity of the brain.
"The literature shows that these tissues exchange substances with each other, but the accumulation of fat in the muscle alters the metabolism of lipids and carbohydrates, and is associated with an increased risk of metabolic syndrome [a group of factors such as high blood pressure, high blood sugar, and altered cholesterol levels], loss of mobility, and dementia," Alexandre explained.
Another key factor identified in the research involves the interaction between abdominal fat, vitamin D deficiency, and memory loss. Excess visceral fat sequesters vitamin D and reduces its circulating availability in the body, triggering a cascade of effects that simultaneously affect the motor system and the central nervous system.
"There's a clear biological cycle: people with more abdominal fat are at greater risk of vitamin D deficiency. Since that hormone is essential for protein synthesis and muscle strength, a deficiency weakens the muscles and reduces muscle mass. At the same time, because it plays a direct role in protecting brain tissue, vitamin D deficiency significantly increases the risk of cognitive decline in older adults," the researcher explained.
AI in the service of public health
To translate these scientific findings into practical care within the SUS (the "Unified Health System," Brazil's national public health network), the Science Center for the Development of Intelligent Methods in the SUS for the Treatment of People with Dementia (CCD-MIDEM) was recently established at UFSCar with support from FAPESP. The initiative uses artificial intelligence tools and biomarkers to integrate data from electronic health records and imaging tests into specialized care for older people.
"Public services face enormous difficulty in making early and differential diagnoses of types of dementia, such as vascular dementia and Alzheimer's disease. With artificial intelligence, we aim to create predictive models capable of indicating the probability of dementia during the first consultations and defining the most appropriate multidisciplinary intervention for each stage of the disease," Alexandre emphasized.
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