Tomkova, K. orcid.org/0000-0002-9032-2366, Roman, M., Adebayo, A.S. orcid.org/0000-0002-7008-0531 et al. (13 more authors) (2024) Multimorbidity is associated with myocardial DNA damage, nucleolar stress, dysregulated energy metabolism, and senescence in cardiovascular disease. npj Aging, 10. 58. ISSN 2731-6068
Abstract
This study investigates why individuals with multimorbidity—two or more chronic conditions—are more prone to adverse outcomes after surgery. In our cohort, ninety-eight of 144 participants had multimorbidity. The myocardial transcriptome and metabolites involved in energy production were measured in 53 and 57 sequential participants, respectively. Untargeted analysis of the metabolome in blood and myocardium was performed in 30 sequential participants. Mitochondrial respiration in circulating mononuclear cells was measured in 70 participants. Results highlighted four main biological processes associated with multimorbidity: DNA damage with epigenetic changes, mitochondrial energy disruption, cellular aging (senescence) and innate immune response. Histone 2B, its ubiquitination enzymes and AKT3 were upregulated in the multimorbid group. Plasma senescence-associated proteins (IL-1β, GM-CSF) increased with more comorbidities. DNA damage and nucleolar instability were specifically apparent in multimorbid myocardium. We conclude that multimorbidity in cardiovascular patients accelerates biological aging, making them more vulnerable to metabolic stress.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Cardiovascular diseases; Mitochondria; Senescence |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Jan 2025 10:51 |
Last Modified: | 20 Jan 2025 10:51 |
Published Version: | https://doi.org/10.1038/s41514-024-00183-z |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1038/s41514-024-00183-z |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221535 |