Hepatic Hydrogen Sulfide Levels Reduced in Mouse Model of Hutchinson-Gilford Progeria Syndrome | Aging-US

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Aging-US published this research paper on June 23, 2023, in Volume 15, Issue 12, entitled, “Hepatic hydrogen sulfide levels are reduced in mouse model of Hutchinson-Gilford progeria syndrome" by researchers from the Glasgow Ageing Research Network (GARNER), School of Biodiversity, One Health and Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK; Molecular Metabolism Group, University/BHF Centre for Cardiovascular Sciences, Queens Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK; Department of Biochemistry and Molecular Biology, Edward A. Doisy Research Center, Saint Louis University School of Medicine, MO; Division of Molecular Metabolism, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna 171 65, Sweden. DOI - https://doi.org/10.18632/aging.204835 Corresponding author - Colin Selman - colin.selman@glasgow.ac.uk, and Stephen E. Wilkie - stephen.wilkie@ki.se 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. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204835 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, progeria, hydrogen sulfide, high-fat diet, ageing, lamin A About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM