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 dynamic response 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 (P ET CO₂) were continuously recorded. In 164 participants, we analyzed the dynamic responses to exercise 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, P ET CO₂, 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 P ET CO₂ throughout exercise. Granger causality analysis revealed bidirectional coupling among MCAv, HR, MAP, and P ET CO₂. Prior P ET CO₂ levels significantly predicted MCAv while MAP had both short- and long-lag predictive effects on MCAv. MCAv also influenced subsequent changes in MAP and P ET CO₂, indicating feedback regulation. P ET CO₂ 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.