Projects per year
Abstract
Age-related diseases account for a high proportion of the total global burden of disease. Despite recent advances in understanding their molecular basis, there is a lack of suitable early biomarkers to test selected compounds and accelerate their translation to clinical trials. We have investigated the utility of in vivo stress reporter systems as surrogate early biomarkers of the degenerative disease progression. We hypothesized that cellular stress observed in models of human degenerative disease preceded overt cellular damage and at the same time will identify potential cytoprotective pathways. To test this hypothesis, we generated novel accelerated ageing (progeria) reporter mice by crossing the LmnaG609G mice into our oxidative stress/inflammation (Hmox1) and DNA damage (p21) stress reporter models. Histological analysis of reporter expression demonstrated a time-dependent and tissue-specific activation of the reporters in tissues directly associated with Progeria, including smooth muscle cells, the vasculature and gastrointestinal tract. Importantly, reporter expression was detected prior to any perceptible deleterious phenotype. Reporter expression can therefore be used as an early marker of progeria pathogenesis and to test therapeutic interventions. This work also demonstrates the potential to use stress reporter approaches to study and find new treatments for other degenerative diseases.
Original language | English |
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Pages (from-to) | 5463-5472 |
Number of pages | 10 |
Journal | Journal of Cellular and Molecular Medicine |
Volume | 26 |
Issue number | 21 |
Early online date | 6 Oct 2022 |
DOIs | |
Publication status | Published - Nov 2022 |
Keywords
- accelerated ageing
- early biomarker
- preclinical model
- progeria
- stress pathways
ASJC Scopus subject areas
- Molecular Medicine
- Cell Biology
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Dive into the research topics of 'In vivo stress reporters as early biomarkers of the cellular changes associated with progeria'. Together they form a unique fingerprint.Projects
- 3 Finished
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Preclinical Platform to Predict Therapeutic Benefit in Accelerated Ageing
Henderson, C. (Investigator) & Inesta-Vaquera, F. (Investigator)
15/04/19 → 14/07/21
Project: Research
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Defining the Deleterious Effects of Environmental Pollutants at a Mechanistic Level (Joint with Queen Mary, University of London)
Henderson, C. (Investigator) & Wolf, R. (Investigator)
1/12/17 → 30/11/21
Project: Research
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A Next-generation Platform for Catalysing Pre-clinical Development of Drugs against Alzheimer's and other Degenerative Diseases of Old-age (NEW-AGE)
McMahon, M. (Investigator) & Wolf, R. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
1/02/17 → 31/07/18
Project: Research