Simple Blood Test Identifies Metabolic Signature of Healthier Aging

Exercise has long been known to protect mobility and reduce the risk of chronic disease, but the molecular processes that translate activity into healthier aging have remained unclear. Researchers have studied whether the benefits of an active lifestyle could be seen directly in blood and whether specific molecules could serve as markers of fitness. Now, a new study shows that a simple blood test, combined with advanced analytics, can track how well someone is aging and identify key metabolites linked to physical performance.

A research team from the University of Vienna (Vienna, Austria), in collaboration with Nankai University (Tianjin, China), has developed a method that merges metabolomics with machine learning and a novel modeling tool. They first created a Body Activity Index (BAI) from physical tests and a Metabolomics Index from blood concentrations of 35 metabolites. The approach captures both endurance and molecular signals, providing a comprehensive measure of active aging at the systemic level.

Image: Researchers have linked physical fitness to blood biomarkers, with aspartate emerging as a key player (Photo courtesy of University of Vienna)

The study analyzed 263 samples from older adults and found a strong correlation between the two indices, with a Pearson coefficient of 0.85. Five machine-learning models were trained to classify active versus less-active groups, with boosting methods achieving over 91% accuracy (AUC > 0.91). Across all models, eight metabolites consistently predicted activity, with aspartate emerging as the dominant biomarker of physical fitness.

To explore how these molecules interact, the team applied COVRECON, a network modeling tool that reconstructs biochemical connections. The analysis identified aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as central hubs in metabolic rewiring, validated through standard blood tests. Active participants showed greater fluctuations in AST and ALT over six months, suggesting enhanced metabolic flexibility in liver and muscle function.

The findings, published in npj Systems Biology and Applications, also connect fitness to brain health, as aspartate plays a dual role as a neurotransmitter precursor, influencing learning and memory. Low AST and ALT levels or elevated ratios have been linked to a higher risk of Alzheimer’s disease and cognitive decline. By linking activity-driven metabolic shifts to brain resilience, the study suggests that blood-based biomarkers could one day track both physical and cognitive aging.

“Physical activity does more than building up muscle mass. It rewires our metabolism at the molecular level. By decoding those changes, we can track – and even guide—how well someone is aging,” said Wolfram Weckwerth, professor at the University of Vienna.

Related Links:
University of Vienna
Nankai University