RT Journal Article
T1 Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution
A1 Ramos-Marquès, Estel
A1 García-Mendívil, Laura
A1 Pérez-Zabalza, María
A1 Santander-Badules, Hazel
A1 Srinivasan, Sabarathinam
A1 Oliveros, Juan Carlos
A1 Torres-Pérez, Rafael
A1 Cebollada, Alberto
A1 Vallejo-Gil, José María
A1 Fresneda-Roldán, Pedro Carlos
A1 Fañanás-Mastral, Javier
A1 Vázquez-Sancho, Manuel
A1 Matamala-Adell, Marta
A1 Sorribas-Berjón, Juan Fernando
A1 Bellido-Morales, Javier André
A1 Mancebón-Sierra, Francisco Javier
A1 Vaca-Núñez, Alexánder Sebastián
A1 Ballester-Cuenca, Carlos
A1 Jiménez-Navarro, Manuel
A1 Villaescusa, José Manuel
A1 Garrido-Huéscar, Elisa
A1 Segovia-Roldán, Margarita
A1 Oliván-Viguera, Aida
A1 Gómez-González, Carlos
A1 Muñiz, Gorka
A1 Diez, Emiliano
A1 Ordovás, Laura
A1 Pueyo, Esther
K1 Biological aging
K1 Biomarkers
K1 Gene regulation network
K1 Heart aging
K1 microRNA
K1 Transcriptomic age marker
K1 Transcriptome
K1 Living donors
K1 Myocardium
K1 Heart ventricles
K1 Envejecimiento
K1 Biomarcadores
K1 Redes reguladoras de genes
K1 MicroARNs
K1 Transcriptoma
K1 Donadores vivos
K1 Miocardio
K1 Ventrículos cardíacos
AB 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.
PB Wiley-Blackwell Publishing Ltd.
SN 1474-9718
YR 2021
FD 2021-06-06
LK http://hdl.handle.net/10668/4586
UL http://hdl.handle.net/10668/4586
LA en
NO Ramos-Marquès E, García-Mendívil L, Pérez-Zabalza M, Santander-Badules H, Srinivasan S, Oliveros JC, et al. Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution. Aging Cell. 2021 Jul;20(7):e13383
DS RISalud
RD Apr 5, 2025