title: Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria.
abstract: Hutchinson-Gilford progeria syndrome (HGPS), a fatal premature aging disease, is caused by a single-nucleotide mutation in the LMNA gene. Previous reports have focused on nuclear phenotypes in HGPS cells, yet the potential contribution of the mitochondria, a key player in normal aging, remains unclear. Using high-resolution microscopy analysis, we demonstrated a significantly increased fraction of swollen and fragmented mitochondria and a marked reduction in mitochondrial mobility in HGPS fibroblast cells. Notably, the expression of PGC-1α, a central regulator of mitochondrial biogenesis, was inhibited by progerin. To rescue mitochondrial defects, we treated HGPS cells with a mitochondrial-targeting antioxidant methylene blue (MB). Our analysis indicated that MB treatment not only alleviated the mitochondrial defects but also rescued the hallmark nuclear abnormalities in HGPS cells. Additional analysis suggested that MB treatment released progerin from the nuclear membrane, rescued perinuclear heterochromatin loss and corrected misregulated gene expression in HGPS cells. Together, these results demonstrate a role of mitochondrial dysfunction in developing the premature aging phenotypes in HGPS cells and suggest MB as a promising therapeutic approach for HGPS.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Zheng-Mei
authors.initials: ZM
authors.lastname: Xiong
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.|Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Haoyue
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Zeshan
authors.initials: Z
authors.lastname: Tariq
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Eunae
authors.initials: E
authors.lastname: Ko
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: LaDana
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sesaki
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Kan
authors.initials: K
authors.lastname: Cao
mesh_terms: D019588:Aging, Premature / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008751:Methylene Blue / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011371:Progeria / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008751:Methylene Blue
keywords: PGC1-α; aging; methylene blue; mitochondria; progeria