2026-05-22T17:24:40Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/183672024-11-28T14:52:28Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16973

00925njm 22002777a 4500 dc Ramos-Marquès, Estel author García-Mendívil, Laura author Pérez-Zabalza, María author Santander-Badules, Hazel author Srinivasan, Sabarathinam author Oliveros, Juan Carlos author Torres-Pérez, Rafael author Cebollada, Alberto author Vallejo-Gil, José María author Fresneda-Roldán, Pedro Carlos author Fañanás-Mastral, Javier author Vázquez-Sancho, Manuel author Matamala-Adell, Marta author Sorribas-Berjón, Juan Fernando author Bellido-Morales, Javier André author Mancebón-Sierra, Francisco Javier author Vaca-Núñez, Alexánder Sebastián author Ballester-Cuenca, Carlos author Jiménez-Navarro, Manuel author Villaescusa, José Manuel author Garrido-Huéscar, Elisa author Segovia-Roldán, Margarita author Oliván-Viguera, Aida author Gómez-González, Carlos author Muñiz, Gorka author Diez, Emiliano author Ordovás, Laura author Pueyo, Esther author 2021-06-06 Aging is the main risk factor for cardiovascular diseases. In humans, cardiac aging remains poorly characterized. Most studies are based on chronological age (CA) and disregard biological age (BA), the actual physiological age (result of the aging rate on the organ structure and function), thus yielding potentially imperfect outcomes. Deciphering the molecular basis of ventricular aging, especially by BA, could lead to major progresses in cardiac research. We aim to describe the transcriptome dynamics of the aging left ventricle (LV) in humans according to both CA and BA and characterize the contribution of microRNAs, key transcriptional regulators. BA is measured using two CA-associated transcriptional markers: CDKN2A expression, a cell senescence marker, and apparent age (AppAge), a highly complex transcriptional index. Bioinformatics analysis of 132 LV samples shows that CDKN2A expression and AppAge represent transcriptomic changes better than CA. Both BA markers are biologically validated in relation to an aging phenotype associated with heart dysfunction, the amount of cardiac fibrosis. BA-based analyses uncover depleted cardiac-specific processes, among other relevant functions, that are undetected by CA. Twenty BA-related microRNAs are identified, and two of them highly heart-enriched that are present in plasma. We describe a microRNA-gene regulatory network related to cardiac processes that are partially validated in vitro and in LV samples from living donors. We prove the higher sensitivity of BA over CA to explain transcriptomic changes in the aging myocardium and report novel molecular insights into human LV biological aging. Our results can find application in future therapeutic and biomarker research. 10.1111/acel.13383 1474-9726 1474-9718 Aging Cell http://hdl.handle.net/10668/4586 34092006 http://hdl.handle.net/20.500.12105/18367 Biological aging Biomarkers Gene regulation network Heart aging microRNA Transcriptomic age marker Transcriptome Living donors Myocardium Heart ventricles Envejecimiento Biomarcadores Redes reguladoras de genes MicroARNs Transcriptoma Donadores vivos Miocardio Ventrículos cardíacos Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution