Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria

Zheng Mei Xiong, Ji Young Choi, Kun Wang, Haoyue Zhang, Zeshan Tariq, Di Wu, Eunae Ko, Christina Ladana, Hiromi Sesaki, Kan Cao

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)279-290
Number of pages12
JournalAging Cell
Volume15
Issue number2
DOIs
StatePublished - Apr 1 2016

Keywords

  • Aging
  • Methylene blue
  • Mitochondria
  • PGC1-α
  • Progeria

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint Dive into the research topics of 'Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria'. Together they form a unique fingerprint.

Cite this