Ghrelin delays premature aging in Hutchinson-Gilford progeria syndrome
Ghrelin delays premature aging in Hutchinson-Gilford progeria syndrome
Abstract Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition arising from a single nucleotide alteration in the LMNA gene, which leads to the production of a defective lamin A protein known as progerin. The buildup of progerin hastens the onset of premature and expedited aging. Patients with HGPS exhibit short stature, low body weight, lipodystrophy, metabolic dysfunction, and skin and musculoskeletal abnormalities and, in most cases, die of cardiovascular disease by their early teenage years. Currently, no effective cure or treatment for the disease highlights the importance of discovering new therapeutic strategies. Herein, we present evidence that the hormone ghrelin, besides promoting autophagy and progerin clearance, rescued several cellular hallmarks of premature aging of human HGPS fibroblasts. Using an HGPS mouse model, LmnaG609G/G609G mice, we also show that ghrelin administration rescued the short-lived mice molecular and histopathological progeroid features, prevented progressive weight loss at later stages, reverted the lipodystrophic phenotype, and extended lifespan. Thus, we disclose that modulation of ghrelin signaling may give rise to new treatment targets and translational approaches that may improve outcomes and the health quality of HGPS patients and natural aging pathologies.
Ferreira-Marques Marisa、Nissan Xavier、Cavadas Cl¨￠udia、Aveleira C¨|lia A.、Lucas Vasco、L¨?pez-Ot¨an Carlos、Botelho Mariana、Cortes Lu¨asa、de Almeida Lu¨as Pereira、Carvalho Andr¨|、Carmo-Silva Sara、Real Ana Carolina、Leal Ana、Franco Ana Catarina、¨￠guas Rodolfo
CNC - Center for Neuroscience and Cell Biology, University of Coimbra||CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra||Faculty of Pharmacy, University of CoimbraCECS||INSERM U861||UEVE U861CNC - Center for Neuroscience and Cell Biology, University of Coimbra||CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra||Faculty of Pharmacy, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of Coimbra||CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra||MIA-Portugal - Multidisciplinar Institute of Ageing, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of CoimbraDepartamento de Bioqu¨amica y Biolog¨aa Molecular, Facultad de Medicina, Instituto Universitario de Oncolog¨aa, Universidad de OviedoCNC - Center for Neuroscience and Cell Biology, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of Coimbra||CIBB - Center for Innovative Biomedicine and Biotechnology, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of Coimbra||CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra||Faculty of Pharmacy, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of Coimbra||CIBB - Center for Innovative Biomedicine and Biotechnology, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of Coimbra||CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra||Faculty of Pharmacy, University of CoimbraCNC - Center for Neuroscience and Cell Biology, University of Coimbra
基础医学生理学遗传学
Human agingProgeriaSenescence GhrelinAutophagy
Ferreira-Marques Marisa,Nissan Xavier,Cavadas Cl¨￠udia,Aveleira C¨|lia A.,Lucas Vasco,L¨?pez-Ot¨an Carlos,Botelho Mariana,Cortes Lu¨asa,de Almeida Lu¨as Pereira,Carvalho Andr¨|,Carmo-Silva Sara,Real Ana Carolina,Leal Ana,Franco Ana Catarina,¨￠guas Rodolfo.Ghrelin delays premature aging in Hutchinson-Gilford progeria syndrome[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2023.05.02.539084.点此复制
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