Age Alters Integrated Cerebrovascular and Cardiovascular Dynamic Responses to Exercise: Insights from a Systems Modeling Approach.

Understanding the dynamic interaction between cardiovascular and cerebrovascular systems during exercise is essential to evaluate the mechanisms supporting brain perfusion. This study examined age- and sex-specific differences in cardiovascular and cerebrovascular kinetics and used systems modeling to assess physiological coupling during moderate intensity exercise. We recruited adults to complete a single session of moderate intensity exercise on a recumbent stepper. Middle cerebral artery blood velocity (MCAv), mean arterial pressure (MAP), heart rate (HR), and end-tidal CO2 (PETCO2) were continuously recorded. In 164 participants, the kinetic profiles were analyzed using mono-exponential modeling and functional data analysis. Granger causality within a subject-specific vector autoregression framework evaluated directional influence among physiological signals. Advancing age was associated with an attenuated dynamic response for MCAv, PETCO2, and HR while MAP was elevated. Older adults exhibited significantly smaller MCAv amplitude and slower time constants than young and middle-aged groups. While sex did not influence overall MCAv, MAP, or HR kinetics, men had significantly higher PETCO2 throughout exercise. Granger causality analysis revealed bidirectional coupling among MCAv, HR, MAP, and PETCO2. Prior PETCO2 levels significantly predicted MCAv while MAP had both short- and long-lag predictive effects on MCAv. MCAv also influenced subsequent changes in MAP and PETCO2, indicating feedback regulation. PETCO2 emerged as a dominant driver of MCAv, though systemic interactions reflect an integrated physiological network with multi-component feedback loops. This study advances understanding of cerebrovascular regulation and highlights the utility of systems modeling during exercise.