Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria. Issue 2 (14th December 2015)

• Record Type: Journal Article
• Authors: Xiong, Zheng‐Mei; Choi, Ji Young; Wang, Kun; Zhang, Haoyue; Tariq, Zeshan; Wu, Di; Ko, Eunae; LaDana, Christina; Sesaki, Hiromi; Cao, Kan
• Is Part Of: Aging cell. Volume 15:Issue 2(2016)
• Page Start: 279
• Page End: 290
• Publication Date: 2015-12-14
• Subjects: aging -- methylene blue -- mitochondria -- PGC1‐α -- progeria; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12434
• Languages: English
• ISSNs: 1474-9718

Abstract

Summary: 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.