Ramos-Marquès, EstelGarcía-Mendívil, LauraPérez-Zabalza, MaríaSantander-Badules, HazelSrinivasan, SabarathinamOliveros, Juan CarlosTorres-Pérez, RafaelCebollada, AlbertoVallejo-Gil, José MaríaFresneda-Roldán, Pedro CarlosFañanás-Mastral, JavierVázquez-Sancho, ManuelMatamala-Adell, MartaSorribas-Berjón, Juan FernandoBellido-Morales, Javier AndréMancebón-Sierra, Francisco JavierVaca-Núñez, Alexánder SebastiánBallester-Cuenca, CarlosJiménez-Navarro, ManuelVillaescusa, José ManuelGarrido-Huéscar, ElisaSegovia-Roldán, MargaritaOliván-Viguera, AidaGómez-González, CarlosMuñiz, GorkaDiez, EmilianoOrdovás, LauraPueyo, Esther2023-01-132023-01-132021-06-06Ramos-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):e133831474-9718http://hdl.handle.net/10668/4586Aging 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Biological agingBiomarkersGene regulation networkHeart agingmicroRNATranscriptomic age markerTranscriptomeLiving donorsMyocardiumHeart ventriclesEnvejecimientoBiomarcadoresRedes reguladoras de genesMicroARNsTranscriptomaDonadores vivosMiocardioVentrículos cardíacosMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::AgingMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Anatomy::Cardiovascular System::Heart::Heart VentriclesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Regulatory Sequences, Nucleic Acid::Gene Regulatory NetworksMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Transcription, Genetic::TranscriptomeMedical Subject Headings::Persons::Persons::Tissue Donors::Living DonorsMedical Subject Headings::Anatomy::Cardiovascular System::Heart::MyocardiumMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk FactorsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Computational Biologyresearch article34092006open access10.1111/acel.133831474-9726PMC8282276