Age alters integrated cerebrovascular and cardiovascular dynamic responses to exercise: insights from a systems modeling approach

Understanding the dynamic interaction between the 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 ([Formula: see text]) 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, [Formula: see text], and HR while MAP was elevated. Older adults exhibited significantly smaller MCAv amplitude and slower time constants than young and middle-aged groups. Although sex did not influence overall MCAv, MAP, or HR kinetics, men had significantly higher [Formula: see text] throughout exercise. Granger causality analysis revealed bidirectional coupling among MCAv, HR, MAP, and [Formula: see text]. Prior [Formula: see text] levels significantly predicted MCAv, while MAP had both short- and long-lag predictive effects on MCAv. MCAv also influenced subsequent changes in MAP and [Formula: see text], indicating feedback regulation. [Formula: see text] emerged as a dominant driver of MCAv, though systemic interactions reflect an integrated physiological network with multicomponent feedback loops. This study advances understanding of cerebrovascular regulation and highlights the utility of systems modeling during exercise.NEW & NOTEWORTHY This study demonstrates strong age effects and minimal sex effects on cerebrovascular and cardiovascular responses to moderate-intensity exercise. Using Granger causality modeling, we confirmed [Formula: see text] as a dominant driver of MCAv and revealed bidirectional feedback among systemic and cerebrovascular variables. These findings highlight the value of systems modeling for uncovering dynamic physiological interactions during exercise and provide new insight into how cerebrovascular regulation changes across the adult lifespan.