{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:33:53Z","timestamp":1768570433721,"version":"3.49.0"},"posted":{"date-parts":[[2025,5,6]]},"group-title":"Rehabilitation Medicine and Physical Therapy","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  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 CO\n                  <jats:sub>2<\/jats:sub>\n                  (P\n                  <jats:sub>ET<\/jats:sub>\n                  CO\n                  <jats:sub>2<\/jats:sub>\n                  ) 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, P\n                  <jats:sub>ET<\/jats:sub>\n                  CO\n                  <jats:sub>2<\/jats:sub>\n                  , 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\n                  <jats:sub>ET<\/jats:sub>\n                  CO\n                  <jats:sub>2<\/jats:sub>\n                  throughout exercise. Granger causality analysis revealed bidirectional coupling among MCAv, HR, MAP, and P\n                  <jats:sub>ET<\/jats:sub>\n                  CO\n                  <jats:sub>2<\/jats:sub>\n                  . Prior P\n                  <jats:sub>ET<\/jats:sub>\n                  CO\n                  <jats:sub>2<\/jats:sub>\n                  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\n                  <jats:sub>ET<\/jats:sub>\n                  CO\n                  <jats:sub>2<\/jats:sub>\n                  , indicating feedback regulation. P\n                  <jats:sub>ET<\/jats:sub>\n                  CO\n                  <jats:sub>2<\/jats:sub>\n                  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.\n                <\/jats:p>","DOI":"10.1101\/2025.05.02.25326897","type":"posted-content","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T15:45:19Z","timestamp":1746546319000},"source":"Crossref","is-referenced-by-count":0,"title":["Age Alters Integrated Cerebrovascular and Cardiovascular Dynamic Responses to Exercise: Insights from a Systems Modeling Approach"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1618-7207","authenticated-orcid":false,"given":"Sandra A.","family":"Billinger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5181-7131","authenticated-orcid":false,"given":"Eric D.","family":"Vidoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keshav","family":"Motwani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3070-7712","authenticated-orcid":false,"given":"Bria L.","family":"Bartsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler","family":"Baldridge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeline","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Shojaie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025050806500955000_2025.05.02.25326897v1.1","doi-asserted-by":"publisher","DOI":"10.1113\/EP086249"},{"key":"2025050806500955000_2025.05.02.25326897v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00314001"},{"key":"2025050806500955000_2025.05.02.25326897v1.3","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1992.72.3.1123"},{"key":"2025050806500955000_2025.05.02.25326897v1.4","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.67.2.744"},{"key":"2025050806500955000_2025.05.02.25326897v1.5","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.151449"},{"key":"2025050806500955000_2025.05.02.25326897v1.6","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00569.2011"},{"key":"2025050806500955000_2025.05.02.25326897v1.7","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1038\/jcbfm.2014.142","article-title":"Acute exercise stress reveals cerebrovascular benefits associated with moderate gains in cardiorespiratory fitness","volume":"34","year":"2014","journal-title":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism"},{"key":"2025050806500955000_2025.05.02.25326897v1.8","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00995.2016"},{"key":"2025050806500955000_2025.05.02.25326897v1.9","doi-asserted-by":"crossref","unstructured":"Ward JL , Craig JC , Liu Y , Vidoni ED , Malesky R , Poole DC , and Billinger SA . 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