Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/116128
DC Field | Value | Language |
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dc.contributor.author | Grilo, Luís F. | - |
dc.contributor.author | Zimmerman, Kip D. | - |
dc.contributor.author | Puppala, Sobha | - |
dc.contributor.author | Chan, Jeannie | - |
dc.contributor.author | Huber, Hillary F. | - |
dc.contributor.author | Li, Ge | - |
dc.contributor.author | Jadhav, Avinash Y. L. | - |
dc.contributor.author | Wang, Benlian | - |
dc.contributor.author | Li, Cun | - |
dc.contributor.author | Clarke, Geoffrey D. | - |
dc.contributor.author | Register, Thomas C. | - |
dc.contributor.author | Oliveira, Paulo J. | - |
dc.contributor.author | et al. | - |
dc.date.accessioned | 2024-08-19T14:45:51Z | - |
dc.date.available | 2024-08-19T14:45:51Z | - |
dc.date.issued | 2024-04 | - |
dc.identifier.uri | https://hdl.handle.net/10316/116128 | - |
dc.description.abstract | Age is a prominent risk factor for cardiometabolic disease, often leading to heart structural and functional changes. However, precise molecular mechanisms underlying cardiac remodeling and dysfunction exclusively resulting from physiological aging remain elusive. Previous research demonstrated age-related functional alterations in baboons, analogous to humans. The goal of this study is to identify early cardiac molecular alterations preceding functional adaptations, shedding light on the regulation of age-associated changes. Unbiased transcriptomics of left ventricle samples are performed from female baboons aged 7.5–22.1 years (human equivalent ≈30–88 years). Weighted-gene correlation network and pathway enrichment analyses are performed, with histological validation. Modules of transcripts negatively correlated with age implicated declined metabolism-oxidative phosphorylation, tricarboxylic acid cycle, glycolysis, and fatty-acid β-oxidation. Transcripts positively correlated with age suggested a metabolic shift toward glucose-dependent anabolic pathways, including hexosamine biosynthetic pathway (HBP). This shift is associated with increased glycosaminoglycan synthesis, modification, precursor synthesis via HBP, and extracellular matrix accumulation, verified histologically. Upregulated extracellular matrix-induced signaling coincided with glycosaminoglycan accumulation, followed by cardiac hypertrophy-related pathways. Overall, these findings revealed a transcriptional shift in metabolism favoring glycosaminoglycan accumulation through HBP before cardiac hypertrophy. Unveiling this metabolic shift provides potential targets for age-related cardiac diseases, offering novel insights into early age-related mechanisms. | pt |
dc.description.sponsorship | This research was funded by the ERDF funds through the Operational Programme for Competitiveness–COMPETE 2020 and national funds by Foundation for Science and Technology under FCT-Post-doctoral Fellowship (SPP, SFRH/BPD/116061/2016), FCT-doctoral Fellowship (LFG, SFRH/BD/5539/2020). National Institutes of Health (NIH) grants U19 AG057758 and P51 OD011133. It was also funded by the European Union (HORIZON-HLTH-2022-STAYHLTH101080329). | pt |
dc.language.iso | eng | pt |
dc.publisher | Wiley Open Access | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04539/2020 | pt |
dc.relation | info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP/04539/2020 | pt |
dc.relation | LA/P/0058/2020 | pt |
dc.rights | openAccess | pt |
dc.subject | Cardiac disease | pt |
dc.subject | Aging | pt |
dc.title | Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Shift in the Left Ventricle Promoting Cardiac Remodelling Through Stimulation of the Hexosaminase Biosynthetic Pathway and Glycosaminoglycans Accumulation. | pt |
dc.type | article | pt |
degois.publication.title | Advanced Science | pt |
dc.date.updated | 2024-08-13T23:36:08Z | - |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/10.1002/advs.202309211 | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | https://doi.org/10.1002/advs.202309211 | - |
dc.description.version | E61A-464E-4AF1 | Susana Pereira | - |
dc.description.version | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.slug | cv-prod-3263417 | - |
dc.date.embargo | 2024-04-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.openairetype | article | - |
item.languageiso639-1 | en | - |
item.fulltext | Com Texto completo | - |
item.cerifentitytype | Publications | - |
crisitem.project.grantno | Center for Innovative Biomedicine and Biotechnology - CIBB | - |
crisitem.project.grantno | Center for Innovative Biomedicine and Biotechnology | - |
crisitem.project.grantno | Center for Innovative Biomedicine and Biotechnology - Associate Laboratory | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-5201-9948 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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Advanced_Science_-_2024_-_Grilo_-_Cardiac_Molecular_Analysis_Reveals_Aginga__Associated_Metabolic_Alterations_Promoting__1_.pdf | 8.79 MB | Adobe PDF | View/Open |
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