Accumulation of DNA damage is increasingly recognized as a factor in vascular aging and in the formation of atherosclerotic lesions, and oxidative stress accelerates DNA injury. Double-strand breaks in DNA are the most severe indicator of DNA damage, though oxidative species can harm DNA in many other ways. Cells respond to oxidative injury by producing a variety of antioxidants and activating systems of DNA repair, especially through upregulating genetic expression of enzymes of the Nrf2-mediated transcription network.
Dietary omega-3 fats have been proven to provide functional benefit to the vascular endothelium, including effects on lipid profiles, vasodilation, blood pressure, and thrombosis. Metabolites of EPA and DHA are known to promote resolution of the immune response, and omega-3-sensing receptors modulate the actions of macrophages during inflammation. Omega-3s additionally influence insulin sensitivity in fat cells and the transformation of surveillance monocytes into active macrophages. Previous research shows that blood levels of omega-3s in individuals with coronary artery disease correspond with reduced telomere attrition, suggesting that dietary adequacy of omega-3 fatty acids may additionally help limit biological aging processes through inhibiting telomere degradation.
In this experiment, human aortic endothelial cells were exposed to hydrogen peroxide, and were subsequently administered EPA, DHA, or no further treatment. The cells were assessed for DNA damage, activation of the Nrf2 antioxidant response network, and for levels of biomarkers of cellular senescence prior to and after exposures. DNA damage at gamma-H2AX gene loci is considered the most crucial biomarker for DNA breakage. Key molecules that initiate DNA repair after activation include ATM (ataxia telangiectasia mutated protein) and DNA-dependent protein kinase. Senescence-associated beta-galactosidase is one of the most widely accepted biomarkers for cellular senescence. Antioxidant enzymes genetically regulated by the master transcription factor Nrf2 (nuclear factor erythroid factor 2-related factor 2) include ferritins, heme oxygenase, peroxidases, superoxide dismutase, thioredoxin reductase, catalase, and quinone reductase.
EPA and DHA Attenuate Stress-Induced Vascular Senescence
Omega-3 fatty acids affect cell membrane function, directly influence immune and metabolic network communications, and directly as well as indirectly modulate genetic regulation of cell, mitochondrial, and DNA repair. These structural and functional roles of omega-3s and their metabolites are crucial for successful aging of cardiovascular tissues that are frequently subjected to environmental and lifestyle-related stresses.