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This interorgan\/tissue crosstalk can accelerate aging-related dysfunction through inflammation, senescence-associated secretome, and metabolic and mitochondrial changes resulting in increased oxidative stress, microvascular dysfunction, cellular reprogramming, and tissue fibrosis. This may also underscore the rising incidence and co-occurrence of multiorgan dysfunction in cardiometabolic aging in the population. Examples include interactions between the heart and the lungs, kidneys, liver, muscles, and brain, among others. However, this phenomenon can also present new translational opportunities for identifying diagnostic biomarkers to define early risks of multiorgan dysfunction, gain mechanistic insights, and help to design precision-directed therapeutic interventions. Indeed, this opens new opportunities for therapeutic development in targeting multiple organs simultaneously to disrupt the crosstalk-driven process of mutual disease acceleration. New therapeutic targets could provide synergistic benefits across multiple organ systems in the same at-risk patient. Ultimately, these approaches may together slow the aging process itself throughout the body. In the future, with patient-centered multisystem coordinated approaches, we can initiate a new paradigm of multiorgan early risk prediction and tailored intervention. With emerging tools including artificial intelligence\u2013assisted risk profiling and novel preventive strategies (eg, RNA-based therapeutics), we may be able to mitigate multiorgan cardiometabolic dysfunction much earlier and, perhaps, even slow the aging process itself.<\/jats:p>","DOI":"10.1161\/circresaha.125.325637","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T18:00:24Z","timestamp":1747936824000},"page":"1286-1305","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Aging at the Crossroads of Organ Interactions: Implications for the Heart"],"prefix":"10.1161","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0033-4479","authenticated-orcid":true,"given":"Ilke","family":"Sen","sequence":"first","affiliation":[{"name":"Department of Physiology, INSERM U955 (Institut national de la sant\u00e9 et de la recherche m\u00e9dicale, Unit\u00e9 955), Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Henri Mondor Hospital, F\u00e9d\u00e9ration Hospitalo-Universitaire (FHU SENCODE), Ecole Universitaire de Recherche LIVE (EUR LIVE), Universit\u00e9 Paris-Est Cr\u00e9teil, France (I. 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