Wilkie, S. E., Marcu, D. E., Carter, R. N., Morton, N. M., Gonzalo, S. and Selman, C. (2023) Hepatic hydrogen sulfide levels are reduced in mouse model of Hutchinson-Gilford progeria syndrome. Aging, 15(12), pp. 5266-5278. (doi: 10.18632/aging.204835) (PMID:37354210) (PMCID:PMC10333079)
![[img]](https://eprints.gla.ac.uk/style/images/fileicons/text.png) |
Text
300618.pdf - Published Version Available under License Creative Commons Attribution. 839kB |
Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a rare human disease characterised by accelerated biological ageing. Current treatments are limited, and most patients die before 15 years of age. Hydrogen sulfide (H2S) is an important gaseous signalling molecule that it central to multiple cellular homeostasis mechanisms. Dysregulation of tissue H2S levels is thought to contribute to an ageing phenotype in many tissues across animal models. Whether H2S is altered in HGPS is unknown. We investigated hepatic H2S production capacity and transcript, protein and enzymatic activity of proteins that regulate hepatic H2S production and disposal in a mouse model of HGPS (G609G mice, mutated Lmna gene equivalent to a causative mutation in HGPS patients). G609G mice were maintained on either regular chow (RC) or high fat diet (HFD), as HFD has been previously shown to significantly extend lifespan of G609G mice, and compared to wild type (WT) mice maintained on RC. RC fed G609G mice had significantly reduced hepatic H2S production capacity relative to WT mice, with a compensatory elevation in mRNA transcripts associated with several H2S production enzymes, including cystathionine-γ-lyase (CSE). H2S levels and CSE protein were partially rescued in HFD fed G609G mice. As current treatments for patients with HGPS have failed to confer significant improvements to symptoms or longevity, the need for novel therapeutic targets is acute and the regulation of H2S through dietary or pharmacological means may be a promising new avenue for research.
| Item Type: | Articles |
|---|---|
| Additional Information: | Funding: SEW was supported through a Medical Research Council Precision Medicine Doctoral Training Program in Precision Medicine to CS and NMM (Reference MR/N013166/1), and DEM was supported through a Wellcome Trust Biomedical Vacation Scholarship to CS (Reference 213310/Z/18/Z). The authors also wish to acknowledge support through a Wellcome Trust New Investigator award (Reference 100981/Z/13/Z) to NMM, and start-up funds from the University of Glasgow (College of Medical, Veterinary and Life Sciences) to CS. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Selman, Professor Colin and Marcu, Diana and Wilkie, Mr Stephen |
| Authors: | Wilkie, S. E., Marcu, D. E., Carter, R. N., Morton, N. M., Gonzalo, S., and Selman, C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Aging |
| Publisher: | Impact Journals |
| ISSN: | 1945-4589 |
| ISSN (Online): | 1945-4589 |
| Published Online: | 23 June 2023 |
| Copyright Holders: | Copyright © 2023 Wilkie et al. |
| First Published: | First published in Aging 15(12): 526-5278 |
| Publisher Policy: | Reproduced under a Creative Commons license |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information