AUTHOR=Fountain William A. , Donega Stefano , Banskota Nirad , Moaddel Ruin , Patel Mona , Zukley Linda , Church Sarah , Bustin Katie , Egan Josephine M. , Walston Jeremy , Ferrucci Luigi 

TITLE=Plasma longitudinal metabolic changes with acute maximal aerobic exercise and one-hour recovery

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1613238

DOI=10.3389/fmolb.2025.1613238

ISSN=2296-889X

ABSTRACT=IntroductionTotal body metabolism continuously adapts to match energy supply with demand. During exercise metabolic alterations occur because skeletal muscles require a continuous supply of newly generated ATP to match the demand of the intensity of the exercise, and products of muscle metabolism must be eliminated. The metabolic and energetic flexibility greatly impact maximum physical fitness and exercise duration, as well as the speed of elimination of metabolism end-products. However, so far, the temporal profiling of metabolomic changes in response to exercise of persons with different fitness levels remains relatively unexplored. This study examined metabolic changes during each person’s peak aerobic exercise and one-hour post-exercise recovery in 29 Baltimore Longitudinal Study of Aging (BLSA) participants.MethodsBlood samples were collected at baseline, and at 3-min intervals during both incremental exercise on a treadmill until exhaustion and during recovery. Participants were classified based on the stage when they reached exhaustion as low fitness (LF, completing up to 3 treadmill incremental stages) or high fitness (HF, completing up to 7 incremental stages). The time course of exercise-associated changes in the circulating metabolome were mapped and unique metabolomic trajectories were identified with likelihood-ratio testing and hierarchical clustering.ResultsThe HF group had rapid clearance of bile and amino acids at exercise onset, along with effective clearance of triacylglycerols and glycerophospholipids during recovery. In contrast, the LF group had much reduced clearance of these metabolites and had persistent elevation of triacylglycerols and glycerophospholipids.DiscussionThese findings highlight differences in bile acid clearance and purine metabolism in people of differing fitness levels and provide novel insights into the role of metabolic adaptive responses to aerobic exercise assessed through circulating metabolomic measures.