000109495 001__ 109495
000109495 005__ 20231006143306.0
000109495 0247_ $$2doi$$a10.1111/acel.13383
000109495 0248_ $$2sideral$$a125691
000109495 037__ $$aART-2021-125691
000109495 041__ $$aeng
000109495 100__ $$0(orcid)0000-0002-9218-6062$$aRamos Marquès, Estel
000109495 245__ $$aChronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution
000109495 260__ $$c2021
000109495 5060_ $$aAccess copy available to the general public$$fUnrestricted
000109495 5203_ $$aAging is the main risk factor for cardiovascular diseases. In humans, cardiac aging remains poorly characterized. Most studies are based on chronological age (CA) and disregard biological age (BA), the actual physiological age (result of the aging rate on the organ structure and function), thus yielding potentially imperfect outcomes. Deciphering the molecular basis of ventricular aging, especially by BA, could lead to major progresses in cardiac research. We aim to describe the transcriptome dynamics of the aging left ventricle (LV) in humans according to both CA and BA and characterize the contribution of microRNAs, key transcriptional regulators. BA is measured using two CA-associated transcriptional markers: CDKN2A expression, a cell senescence marker, and apparent age (AppAge), a highly complex transcriptional index. Bioinformatics analysis of 132 LV samples shows that CDKN2A expression and AppAge represent transcriptomic changes better than CA. Both BA markers are biologically validated in relation to an aging phenotype associated with heart dysfunction, the amount of cardiac fibrosis. BA-based analyses uncover depleted cardiac-specific processes, among other relevant functions, that are undetected by CA. Twenty BA-related microRNAs are identified, and two of them highly heart-enriched that are present in plasma. We describe a microRNA-gene regulatory network related to cardiac processes that are partially validated in vitro and in LV samples from living donors. We prove the higher sensitivity of BA over CA to explain transcriptomic changes in the aging myocardium and report novel molecular insights into human LV biological aging. Our results can find application in future therapeutic and biomarker research.
000109495 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000109495 590__ $$a11.005$$b2021
000109495 592__ $$a2.751$$b2021
000109495 594__ $$a13.8$$b2021
000109495 591__ $$aGERIATRICS & GERONTOLOGY$$b4 / 54 = 0.074$$c2021$$dQ1$$eT1
000109495 593__ $$aCell Biology$$c2021$$dQ1
000109495 591__ $$aCELL BIOLOGY$$b30 / 195 = 0.154$$c2021$$dQ1$$eT1
000109495 593__ $$aAging$$c2021$$dQ1
000109495 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000109495 700__ $$0(orcid)0000-0002-2954-1068$$aGarcía Mendívil, Laura$$uUniversidad de Zaragoza
000109495 700__ $$0(orcid)0000-0002-3194-7796$$aPérez Zabalza, María$$uUniversidad de Zaragoza
000109495 700__ $$aSantander Badules, Hazel
000109495 700__ $$aSrinivasan, Sabarathinam
000109495 700__ $$aOliveros, Juan Carlos
000109495 700__ $$aTorres Pérez, Rafael
000109495 700__ $$aCebollada, Alberto
000109495 700__ $$aVallejo Gil, José María
000109495 700__ $$aFresneda Roldán, Pedro Carlos
000109495 700__ $$aFañanás Mastral, Javier
000109495 700__ $$aVázquez Sancho, Manuel
000109495 700__ $$aMatamala Adell, Marta
000109495 700__ $$aSorribas Berjón, Juan Fernando
000109495 700__ $$aBellido Morales, Javier André
000109495 700__ $$aMancebón Sierra, Francisco Javier
000109495 700__ $$aVaca Núñez, Alexánder Sebastián
000109495 700__ $$aBallester Cuenca, Carlos
000109495 700__ $$aJiménez Navarro, Manuel
000109495 700__ $$aVillaescusa, José Manuel
000109495 700__ $$aGarrido Huéscar, Elisa$$uUniversidad de Zaragoza
000109495 700__ $$aSegovia Roldán, Margarita
000109495 700__ $$0(orcid)0000-0001-5348-924X$$aOliván Viguera, Aida
000109495 700__ $$aGómez González, Carlos
000109495 700__ $$aMuñiz, Gorka
000109495 700__ $$aDiez, Emiliano
000109495 700__ $$0(orcid)0000-0003-3982-1263$$aOrdovás, Laura
000109495 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, Esther$$uUniversidad de Zaragoza
000109495 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000109495 773__ $$g20, 7 (2021), 13383 [16 pp.]$$pAging Cell$$tAGING CELL$$x1474-9718
000109495 8564_ $$s2644528$$uhttps://zaguan.unizar.es/record/109495/files/texto_completo.pdf$$yVersión publicada
000109495 8564_ $$s2097692$$uhttps://zaguan.unizar.es/record/109495/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000109495 909CO $$ooai:zaguan.unizar.es:109495$$particulos$$pdriver
000109495 951__ $$a2023-10-06-14:08:24
000109495 980__ $$aARTICLE