Mitochondrial dysfunction is a possible cause of accelerated senescence of mesothelial cells exposed to high glucose
Krzysztof Ksiazek1, João F Passos, Sharon Olijslagers
1Department of Pathophysiology, University of Medical Sciences, Swiecickiego 6, 60781 Poznań, Poland.
Abstract:
High glucose has been found to accelerate cell senescence in vitro. The exact mechanism of this effect is, however, still poorly understood. In this paper we show that human peritoneal mesothelial cells (HPMCs) propagated under high (30mM) glucose were characterized by higher density of DNA double-strand breaks than cells exposed to standard (5mM) glucose concentration. Under both low and high glucose conditions, the vast majority of DNA damage localized to non-telomeric regions of the genome. Moreover, exposure to high glucose resulted in increased accumulation of lipofuscin, increased production of superoxides and peroxides as well as reduced mitochondrial membrane potential and increased mitochondrial mass. Treatment of cells with the free radical scavenger PBN partially rescued the premature senescence caused by high glucose. Together, these results indicate that high glucose may accelerate senescence of HPMCs by impairing mitochondrial function, resulting in overproduction of reactive oxygen species and extensive DNA damage.
Insights
High glucose accelerates human peritoneal mesothelial cell senescence by causing DNA damage and impairing mitochondrial function. Free radical scavengers partially reversed this premature aging, indicating oxidative stress is a key factor.
Area of Science:
- Cell Biology
- Biochemistry
- Gerontology
Background:
- High glucose levels are known to accelerate cellular senescence in vitro.
- The precise mechanisms underlying high glucose-induced senescence remain incompletely understood.
Purpose of the Study:
- To investigate the mechanism by which high glucose accelerates senescence in human peritoneal mesothelial cells (HPMCs).
- To determine the role of DNA damage and mitochondrial dysfunction in this process.
Main Methods:
- HPMCs were cultured under high (30mM) and standard (5mM) glucose conditions.
- DNA double-strand breaks, lipofuscin accumulation, superoxide/peroxide production, mitochondrial membrane potential, and mitochondrial mass were assessed.
- Cells were treated with the free radical scavenger PBN.
Main Results:
- High glucose significantly increased DNA double-strand breaks in HPMCs, primarily in non-telomeric regions.
- Exposure to high glucose led to increased lipofuscin, superoxide, and peroxide production, with reduced mitochondrial membrane potential and increased mitochondrial mass.
- PBN treatment partially rescued cells from high glucose-induced premature senescence.
Conclusions:
- High glucose accelerates HPMC senescence through impaired mitochondrial function and subsequent reactive oxygen species overproduction.
- Extensive DNA damage is a key consequence of this process.
- Targeting oxidative stress may offer a therapeutic strategy against high glucose-induced cellular senescence.
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