109495 20231006143306.0 doi 10.1111/acel.13383 sideral 125691 ART-2021-125691 eng Ramos Marquès, Estel (orcid)0000-0002-9218-6062 Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution 2021 Access copy available to the general public Unrestricted 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. info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 11.005 2021 GERIATRICS & GERONTOLOGY 4 / 54 = 0.074 2021 Q1 T1 CELL BIOLOGY 30 / 195 = 0.154 2021 Q1 T1 2.751 2021 Cell Biology 2021 Q1 Aging 2021 Q1 13.8 2021 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion García Mendívil, Laura Universidad de Zaragoza (orcid)0000-0002-2954-1068 Pérez Zabalza, María Universidad de Zaragoza (orcid)0000-0002-3194-7796 Santander Badules, Hazel Srinivasan, Sabarathinam Oliveros, Juan Carlos Torres Pérez, Rafael Cebollada, Alberto Vallejo Gil, José María Fresneda Roldán, Pedro Carlos Fañanás Mastral, Javier Vázquez Sancho, Manuel Matamala Adell, Marta Sorribas Berjón, Juan Fernando Bellido Morales, Javier André Mancebón Sierra, Francisco Javier Vaca Núñez, Alexánder Sebastián Ballester Cuenca, Carlos Jiménez Navarro, Manuel Villaescusa, José Manuel Garrido Huéscar, Elisa Universidad de Zaragoza Segovia Roldán, Margarita Oliván Viguera, Aida (orcid)0000-0001-5348-924X Gómez González, Carlos Muñiz, Gorka Diez, Emiliano Ordovás, Laura (orcid)0000-0003-3982-1263 Pueyo, Esther Universidad de Zaragoza (orcid)0000-0002-1960-407X 5008 800 Universidad de Zaragoza Dpto. Ingeniería Electrón.Com. Área Teoría Señal y Comunicac. 20, 7 (2021), 13383 [16 pp.] Aging Cell AGING CELL 1474-9718 2644528 http://zaguan.unizar.es/record/109495/files/texto_completo.pdf Versión publicada 2097692 http://zaguan.unizar.es/record/109495/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:109495 articulos driver 2023-10-06-14:08:24 ARTICLE