Ageing – oxidative stress, PTMs and disease

Ebert, T., Tran, N. , Schurgers, L., Stenvinkel, P. and Shiels, P. G. (2022) Ageing – oxidative stress, PTMs and disease. Molecular Aspects of Medicine, 86, 101099. (doi: 10.1016/j.mam.2022.101099) (PMID:35689974)

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Post-translational modifications (PTMs) have been proposed as a link between the oxidative stress-inflammation-ageing trinity, thereby affecting several hallmarks of ageing. Phosphorylation, acetylation, and ubiquitination cover >90 of all the reported PTMs. Several of the main PTMs are involved in normal “healthy” ageing and in different age-related diseases, for instance neurodegenerative, metabolic, cardiovascular, and bone diseases, as well as cancer and chronic kidney disease. Ultimately, data from human rare progeroid syndromes, but also from long-living animal species, imply that PTMs are critical regulators of the ageing process. Mechanistically, PTMs target epigenetic and non-epigenetic pathways during ageing. In particular, epigenetic histone modification has critical implications for the ageing process and can modulate lifespan. Therefore, PTM-based therapeutics appear to be attractive pharmaceutical candidates to reduce the burden of ageing-related diseases. Several phosphorylation and acetylation inhibitors have already been FDA-approved for the treatment of other diseases and offer a unique potential to investigate both beneficial effects and possible side-effects. As an example, the most well-studied senolytic compounds dasatinib and quercetin, which have already been tested in Phase 1 pilot studies, also act as kinase inhibitors, targeting cellular senescence and increasing lifespan. Future studies need to carefully determine the best PTM-based candidates for the treatment of the “diseasome of ageing”.

Item Type:Articles
Additional Information:Impact of post-translational modification on the genesis and progression of diseases. Funding: TE was supported by a Novo Nordisk postdoctoral fellowship run in partnership with Karolinska Institutet, Stockholm, Sweden, a Karolinska Institutet Research Foundation grant, as well as by the EFSD Mentorship Programme supported by AstraZeneca. The study also benefited from generous support from the Swedish Heart and Lung Foundation (20160384), the Strategic Research Programme in Diabetes at Karolinska Institutet (Swedish Research Council grant No 2009-1068), and the Stockholm City Council (ALF). PS and TE were further supported by Njurfonden (Swedish Kidney Foundation). PGS was supported by awards from 4D Pharma and Constant Pharma. Ngoc Tran is supported by MINDSHIFT — H2020-MSCA-ITN-2020, Grant Agreement number: 954798.
Keywords:Healthy ageing, inflammation, nuclear factor erythroid 2-related factor 2, oxidative stress, post-translational modifications, premature ageing, senescence.
Glasgow Author(s) Enlighten ID:Tran, Ms Ngoc and Shiels, Professor Paul
Authors: Ebert, T., Tran, N., Schurgers, L., Stenvinkel, P., and Shiels, P. G.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Molecular Aspects of Medicine
ISSN (Online):1872-9452
Published Online:08 June 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Molecular Aspects of Medicine 86:101099
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
310295MINDSHIFTRhian TouyzEuropean Commission (EC)954798CS - Epigenetics