Inflammation, Lipid (Per)oxidation, and Redox Regulation.

Area of Science:

• Biochemistry
• Immunology
• Gerontology

Background:

• Aging is associated with increased inflammation, mitochondrial dysfunction, and reactive oxygen species (ROS) production.
• Mitochondrial damage from ROS contributes to a cycle of senescence, cytokine release, and impaired energy production.
• Oxidized lipids, including oxidized phospholipids (OxPLs), accumulate during inflammation and influence key redox-sensitive transcription factors.

Purpose of the Study:

• To investigate the role of oxidized lipids in age-related inflammation.
• To explore the potential of targeting the lipidome for therapeutic intervention.
• To understand the relationship between mitochondrial health and inflammatory processes in aging.

Main Methods:

• Mass spectrometric methods were used to identify and quantify oxidized lipids.
• Analysis of the effects of oxidized lipids on redox-sensitive transcription factors (Nrf2, PPARγ, AP1, NF-κB).
• Investigation of the kinetic and spatial resolution of lipid modifications in inflammation.

Main Results:

• Families of oxidized phospholipids, cholesterols, and fatty acids were identified, increasing with inflammation.
• These oxidized lipids modulate the activity of transcription factors involved in redox and inflammatory responses.
• The concentration of oxidized phospholipids influences whether they promote or resolve inflammation.

Conclusions:

• Targeting the formation or accumulation of oxidized biomolecules, especially oxidized lipids, in immune cells and mitochondria shows promise for managing age-related inflammation.
• Restoring redox homeostasis and improving mitochondrial quality control are key to developing a resolving (oxy)lipidome.
• This approach could help prevent or delay age-related inflammation and associated vascular comorbidities.