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Skeletal muscle sarcopenia and hypertrophic cardiomyopathy (HCM) are two distinct yet interrelated conditions, often co\u2010existing in elderly individuals and exacerbating disease progression. Mechanistic understanding of sarcopenia\u2010HCM comorbidity is limited, largely based on clinical correlation analyses and a few available mouse models. To facilitate pathophysiological research and accelerate therapeutic development, a more efficient human\u2010relevant in vitro model is needed. This study presents a human\u2010based sarcopenia\u2010HCM comorbidity model in a multi\u2010organ microphysiological system (MPS) that incorporates primary human hepatocytes, human induced pluripotent stem cells (hiPSC)\u2010derived skeletal muscle and cardiomyocytes. The phenotypes for sarcopenia and HCM were first induced and characterized in single\u2010organ systems, then assembled and analyzed in a multi\u2010organ MPS, maintained in circulated serum\u2010free medium. The functional phenotypes of skeletal muscle, cardiomyocytes, and hepatocytes, as well as inter\u2010organ interactions in this organ\u2010chip system align with clinical reports. This MPS comorbidity platform will enable pathophysiological investigation of sarcopenia, HCM, their comorbidity, and testing of therapeutic efficacy, toxicity, and pharmacokinetics. This study highlights how multi\u2010organ MPS can revolutionize preclinical research as a human\u2010relevant, cost\u2010effective, and ethical alternative for studying comorbidities.<\/jats:p>","DOI":"10.1002\/adbi.70147","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:51:26Z","timestamp":1789645886000},"source":"Crossref","is-referenced-by-count":1,"title":["Development of a Multi\u2010Organ Microphysiological (MPS) Model to Study Age\u2010Related Comorbidities"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3488-6220","authenticated-orcid":false,"given":"Gaurav","family":"Srivastava","sequence":"first","affiliation":[{"name":"Nanoscience Technology Center University of Central Florida  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9583-6676","authenticated-orcid":false,"given":"Aakash","family":"Patel","sequence":"additional","affiliation":[{"name":"Nanoscience Technology Center University of Central Florida  Orlando Florida USA"},{"name":"Hesperos Inc.  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