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Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution

Ramos‐Marquès, Estel ; García‐Mendívil, Laura ; Pérez‐Zabalza, María ; 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 ; Segovia‐Roldán, Margarita ; Oliván‐Viguera, Aida ; Gómez‐González, Carlos ; Muñiz, Gorka ; Diez, Emiliano ; Ordovás, Laura ; Pueyo, Esther

Aging cell, 2021-07, Vol.20 (7), p.e13383-n/a [Periódico revisado por pares]

England: John Wiley & Sons, Inc

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Título:
Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution
Autor: Ramos‐Marquès, Estel ; García‐Mendívil, Laura ; Pérez‐Zabalza, María ; 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 ; Segovia‐Roldán, Margarita ; Oliván‐Viguera, Aida ; Gómez‐González, Carlos ; Muñiz, Gorka ; Diez, Emiliano ; Ordovás, Laura ; Pueyo, Esther
Assuntos: Aging ; Aging - genetics ; Analysis ; Bioinformatics ; biological aging ; biomarkers ; Biomarkers - metabolism ; Cardiovascular diseases ; Coronary artery disease ; Female ; Fibrosis ; gene regulation network ; Genes ; Genetic transcription ; heart aging ; Heart diseases ; Heart Ventricles - metabolism ; Humans ; Male ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Myocardium ; Original ; Original Paper ; Phenotypes ; Physiological aspects ; Risk factors ; Senescence ; Structure-function relationships ; Transcription ; Transcriptomes ; transcriptomic age marker ; Ventricle
É parte de: Aging cell, 2021-07, Vol.20 (7), p.e13383-n/a
Notas: Funding information
This work was supported by the European Research Council through grant ERC‐StG 638284, by Ministerio de Ciencia e Innovación (Spain) (PID2019‐105674RB‐I00), by Gobierno de Aragón (LMP124_18), by Ibercaja (JIUZ‐2017‐TEC‐07) and by European Social Fund and by Gobierno de Aragón (Reference Group BSICoS T39‐20R) cofounded by FEDER 2014–2020 “Building Europe from Aragon.” L.G‐M was supported by a predoctoral fellowship from the Departamento de Ciencia, Universidad y Sociedad del Conocimiento from the Gobierno de Aragón 2016–2020 cofounded by Programa Operativo del Fondo Social Europeo Aragón (C150/2016), EMBO Short‐Term fellowship (7710) and Ibercaja‐CAI Estancias de Investigación IT18/18. E.G‐H was supported by a predoctoral fellowship from the Departamento de Ciencia, Universidad y Sociedad del Conocimiento from the Gobierno de Aragón 2019–2023 (CPT_20_19)
Laura Ordovás and Esther Pueyo contributed equally to this work
Estel Ramos‐Marquès and Laura García‐Mendívil contributed equally to this work
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Descrição: 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. The biological age, measured by transcriptional markers, explains better than the chronological age the transcriptional dynamics of the human aging myocardium. microRNAs that change expression in the aging left ventricle are identified. Such microRNAs potentially regulate genes with cardiac‐specific functions. Cardiac‐enriched microRNAs that increase or decrease with biological age are present in plasma. They are thus candidate biomarkers to represent the biological age of the heart.
Editor: England: John Wiley & Sons, Inc
Idioma: Inglês

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Chronological and biological aging of the human left ventricular myocardium: Analysis of microRNAs contribution

England: John Wiley & Sons, Inc

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